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This study assessed the health risks and toxicity of compounds found in the leachate and exhaust air of non-incineration devices used for hospital waste management. Specifically, it measured the levels of potentially toxic elements and pharmaceutical compounds in two disinfection waste treatment devices—hydroclave with shredder (device A) and autoclave without shredder (device B)—at a hospital in Tehran, Iran. Sampling occurred from October 2022 to March 2023. potentially toxic elements were analyzed using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES), while cytotoxicity was evaluated with an ELISA reader.The results indicated that the exhaust air from device A contained high concentrations of barium (9.80 ± 1.60 µg/m3), zinc (8.60 ± 2.25 µg/m3), and chromium (8.45 ± 2.30 µg/m3). In contrast, barium and zinc were the most abundant potentially toxic elements in device B. Analysis of the leachate from device A showed that nickel and arsenic had the lowest concentrations, while barium, chromium, and zinc had the highest. Additionally, Leachate analysis from Device A also revealed high levels of barium, chromium, and zinc, while nickel and arsenic were found at lower concentrations. Significant concentrations of pharmaceutical compounds, such as azithromycin, ciprofloxacin, diclofenac, and naproxen, were detected in the effluent from both devices, with higher concentrations in Device A, indicating improper segregation and inadequate management of pharmaceutical waste. This underscores the urgent need for continuous training, supervision, and monitoring in pharmaceutical waste management. Cytotoxicity analyses showed that particulate matter and leachate from Device A had a more pronounced negative impact on human cell lines (HepG2 and A549) compared to Device B. Health risk assessments using Monte Carlo simulations indicated that the carcinogenic risks from potentially toxic elements (PTEs) in Device A, particularly arsenic and chromium, exceeded the permissible limits set by the USEPA, while Device B posed significantly lower risks. These findings highlight the importance of educating hospital staff on proper waste segregation, continuous monitoring, and implementing advanced waste management protocols to protect public health and the environment. [ABSTRACT FROM AUTHOR]

The 21st‐century toxicity testing program recommends the use of cytotoxicity data from human cells in culture for rapid in vitro screening focusing on biological pathways of potential toxicants to predict in vivo toxicity. Liver is the major organ for both endogenous and exogenous chemical metabolism of xenobiotics. Therefore, this review was undertaken to evaluate side by side five different currently used commercial cytotoxicity assay kits for purpose of rapid predictive screening of potential hepatotoxicants. The test compounds for this review were selected from the NIH LiverTox and FDA Liver Toxicity Knowledge Base (LTKB) databases. Human liver HepG2, HepaRG, and rat liver Clone 9 cell cultures were used as the in vitro liver models. Five commercial assay kits representing different biomarkers or pathways were selected for this review. These kits are Vita‐Orange Cell Viability Assay Kit (Sigma‐Aldrich), CellTiter‐Glo Cell Viability Assay Kit (Promega), CytoTox‐ONE Homogeneous Membrane Integrity Assay Kit (Promega), DNA Quantitation Fluorescence Assay Kit (Sigma‐Aldrich), and Neutral Red Based In Vitro Toxicology Assay Kit (Sigma‐Aldrich). This review found that these kits can all be used for rapid predictive cytotoxicity screening of potential hepatotoxicants in human liver HepG2 and rat liver Clone 9 cells in culture as in vitro liver models without compromising quality and accuracy of endpoint measurements as well as the length of toxicity screening time. Unraveling the structure–activity relationship of potential hepatotoxins would help to classify their hepatotoxic effects. Therefore, in addition to the current regulatory hepatotoxicity testing strategies, development and regulatory approval of hepatotoxins need to be discussed in order to identify potential gaps in the safety assessment. The overall results of our study support the hypothesis that a battery of rapid, simple, and reliable assays is an excellent tool for predicting in vivo effects of suspected liver toxins. The human liver HepaRG cells do not appear to be an ideal in vitro liver model for this purpose. Five commercial cytotoxicity assay kits used for screening hepatotoxins were evaluated using HepG2, HepaRG, and Clone 9 cell cultures as in vitro models. This study supports the hypothesis that a battery of these assays is an excellent tool for predicting in vivo effects of liver toxins. [ABSTRACT FROM AUTHOR]

Human African trypanosomiasis (HAT) is an infectious disease which kills humans and animals as a result of hematological distortions, oxidative stress, tissue and neuroinflammations. This study reports on the differences in cytotoxicity, antitrypanosomal, antioxidant, and anti‐inflammatory activities of ethanol extracts from Clausena anisata fruit (CFE), Azadirachta indica (neem) leaf (NLE), and stem bark (NSBE), medicinal plants used to treat HAT in its endemic communities. The extracts remarkably inhibited Trypanosoma brucei brucei (GUTat 3.1) parasite in vitro with CFE recording the highest effect with an IC50 of 0.0055 (0.0955) μg/mL. The IC50 of the standard Coptis japonicum was 0.5957 (0.0693) μg/mL. Also, the antitrypanosomal activity of NLE was 123.34% higher than that of NSBE. The percentage number of wells containing viable T. b. brucei parasites was very significantly (p < 0.001) reduced for all the extracts after 48 h of incubation. Furthermore, the extracts did not show cytotoxicity against the liver (HepG2) cells (CC50s > 100 μg/mL and SI = 13.12–32,025.45). NSBE contained the highest quantity of phenolic compounds and flavonoids and also produced the highest antioxidant and anti‐inflammatory activity in the DPPH free radical scavenging assay (IC50 = 4.99 ± 0.018) and protein denaturation assay (IC50 = 0.1805 ± 0.0002 μg/mL). In addition, phytochemical analysis showed that NLE contained the highest number of classes of phytochemical constituents (seven) among the extracts. These results indicate that CFE, NLE, and NSBE possessed significant antitrypanosomal activity as a result of their antioxidant and anti‐inflammatory actions. However, a different mechanism was also involved in the antitrypanosomal activity of CFE and NLE, since their antitrypanosomal activity is greater than NSBE which demonstrated the highest antioxidant and anti‐inflammatory activities. Due to the remarkable antitrypanosomal action of CFE, its constituents are being isolated for possible development into novel antitrypanosomal agents. [ABSTRACT FROM AUTHOR]

The effects of Nano propolis (NP-Pro) alone or combined with radiation in human liver cancer cell line (HepG2) in vitro were evaluated. NP-Pro is made up of natural propolis particles that are between 1 and 100 nm in diameter that have been linked together to increase its effectiveness without altering its original characteristics. Numerous benefits of propolis include its anti-inflammatory, antioxidant, anti-cancer, and antifungal properties. Propolis nanoparticles were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and X-ray diffraction (XRD). Cell viability was examined using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and apoptosis was assessed using flow cytometry. HepG2 was treated with both different concentrations of NP-Pro and irradiated 10 Gy using a 137Cs gamma source. The cytotoxic effect of the studied NP-Pro increased with an increase in concentrations. The IC50 of NP-Pro in the cytotoxicity test with the HepG2 cells in combination with a radiation dose of 10 Gy was 7.58 ± 0.39 µg/mL, while for free NP-Pro, it was 29.58 ± 1.27 µg/mL. The effects of the combined use of NP-Pro and irradiated 10 Gy on cytotoxicity, generation of reactive oxygen species, and activity of apoptosis-mediated signaling pathways were studied on the HepG2 cell line. Cell apoptosis tests have shown that HepG2 cells that are exposed to nano propolis + 10 Gy undergo apoptosis, and their population is dramatically decreased (p < 0.005). All these studies concluded that propolis nanoparticles could be a good alternative to existing anticancer materials in combination with gamma radiation. [ABSTRACT FROM AUTHOR]

Micro/nanoplastics (MP/NP) are pervasive contaminants that are detected throughout the environment in diverse matrices. Exposure to MP/NP have been demonstrated in humans by their presence in numerous body fluids and tissues. Due to the large quantity of production and broad applications, polymethyl methacrylate (PMMA) MP/NP have frequently been measured in surveys of microplastics in the environment. The effects of size, surface charge (aminated, carboxylated or non-functionalized), concentration, and exposure duration of PMMA particles in HepG2 human liver cells were evaluated in this study. The majority of PMMA MP/NP were non-cytotoxic. Some sporadic cytotoxicity was measured but it did not follow discernable trends. Confocal images revealed that 50, 100, and 1000 nm PMMA MP/NP were all taken up by HepG2 cells irrespective of surface charge. Particle size significantly affected caspase-3 release (p = 0.0002). Apoptosis was induced in only a small number of cells at 24 and 48 h for 50 nm and 1000 nm MP/NP. From 72 – 120 h, apoptosis increased in a time dependent manner for 50 nm beads at 100 µg/mL for all three surface functionalizations, with amine beads having the highest apoptosis at 120 h (36 %). Production of the pro-inflammatory interleukin-8 (IL-8) increased > 2x when the duration of exposure increased from 4 to 24 h irrespective of particle size, charge, or concentration. Collectively, PMMA MP/NP were not cytotoxic at the concentrations tested, but were able to translocate into HepG2 cells, release caspase-3, induce apoptosis, and produce IL-8 in a time dependent fashion.

Objective: Nanoplastics (NPs) are consider as emerging persistent environmental pollutants. Widespread distribution of these nanoparticles is a global problem. However, their toxic effects in mammalian tissues and cells remain mainly unknown. This study aims to investigate the cytotoxicity of PET nanoplastics (PET-NPs) in the human hepatocarcinoma (HepG2) cell line. Methods: Toxic effects after 72h of exposure to different concentrations of PET-NPs (10–500 µg/mL) were evaluated by morphological alterations, cell internalization, cell viability (MTT), lactate dehydrogenase (LDH) release assays, induction of oxidative stress (total antioxidant capacity, TAC), and genotoxicity (comet assay). Results: Cell viability reduced at all treatment concentrations in a dose–response manner, and 616.7 µg/mL was determined as IC50. No cell membrane damages detected by LDH assay. TAC reduced significantly after 12 h exposure to > 400 μg/mL PET-NPs. Dose-dependent DNA damages were observed after 72 h. Conclusion: These findings indicated that PET-NPs have significant cytotoxic effects, particularly on genotoxicity and induction of oxidative stress. The results obtained here showed a significant impact of PET-NPs at the tested concentrations suggest a potential impact on humans. Other studies are currently underway to confirm these toxic effects. [ABSTRACT FROM AUTHOR]

To develop the risk prediction technology for mixture toxicity, a reliable and extensive dataset of experimental results is required. However, most published literature only provides data on combinations containing two or three substances, resulting in a limited dataset for predicting the toxicity of complex mixtures. Complex mixtures may have different mode of actions (MoAs) due to their varied composition, posing difficulty in the prediction using conventional toxicity prediction models, such as the concentration addition (CA) and independent action (IA) models. The aim of this study was to generate an experimental dataset comprising complex mixtures. To identify the target complex mixtures, we referred to the findings of the HBM4EU project. We identified three groups of seven to ten components that were commonly detected together in human bodies, namely environmental phenols, perfluorinated compounds, and heavy metal compounds, assuming these chemicals to have different MoAs. In addition, a separate mixture was added consisting of seven organophosphate flame retardants (OPFRs), which may have similar chemical structures. All target substances were tested for cytotoxicity using HepG2 cell lines, and subsequently 50 different complex mixtures were randomly generated with equitoxic mixtures of EC10 levels. To determine the interaction effect, we calculated the model deviation ratio (MDR) by comparing the observed EC10 with the predicted EC10 from the CA model, then categorized three types of interactions: antagonism, additivity, and synergism. Dose–response curves and EC values were calculated for all complex mixtures. Out of 50 mixtures, none demonstrated synergism, while six mixtures exhibited an antagonistic effect. The remaining mixtures exhibited additivity with MDRs ranging from 0.50 to 1.34. Our experimental data have been formatted to and constructed for the database. They will be utilized for further research aimed at developing the combined CA/IA approaches to support mixture risk assessment. [ABSTRACT FROM AUTHOR]

synthesis of a pyrazole containing compound was achieved by reacting phenyl hydrazine with (E)-2-((4- bromophenyl) diazinyl)-1-phenylbutane-1,3-dione to produce 4-((4-bromophenyl) diazinyl)-5-methyl-1,3-diphenylpyrazole and characterization using mass spectrometer, 1H NMR and 13C NMR. The pharmacological evaluation of the synthesized compound, denoted as (KA5), against Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 9027, Staphylococcus aureus ATCC 29213 and Clostridiums sporogeneses ATCC 19404, indicate that there is no promising antibacterial activity. However, KA5 shows a competitive anticancer activity (IC50: 8.5μM) upon its evaluation against hepatocellular carcinoma cell line (HepG 2) compared to sorafenib (IC50: 4.51μM). Moreover, human skin fibroblast (HSF) was used to investigate the effect of KA5 on normal cell lines, (IC50: 5.53μM). The presented biological evaluations resulted in better understanding of structure-activity relationship for 1, 3, 4-trisubstituted pyrazoles and revealed a great opportunity for more investigations for novel pyrazole-containing anticancer agents. [ABSTRACT FROM AUTHOR]

Millions of people around the world are exposed to elevated levels of arsenic through food or drinking water. Epidemiological studies have linked chronic arsenic exposure to an increased risk of several cancers, cardiovascular disease, central nervous system neuropathies, and genotoxic as well as immunotoxic effects. In addition to the induction of oxidative stress and inhibition of DNA repair processes, epigenetic effects, including altered DNA methylation patterns resulting in aberrant gene expression, may contribute to carcinogenicity. However, the underlying mechanisms by which chronic micromolar concentrations of arsenite affect the methylation status of DNA are not fully understood. In this study, human HepG2 hepatocarcinoma cells were treated with 0.5–10 μM sodium arsenite for 24 h, 10, or 20 days. During these periods, the effects on global DNA methylation, cell cycle phase distribution, and gene expression were investigated. While no impact on DNA methylation was seen after short-term exposure, global hypomethylation was observed at both long-term exposure periods, with concomitant induction of the DNA methyltransferase genes DNMT1 and DNMT3B, while DNMT3A was slightly down-regulated. Pronounced time- and concentration-dependent effects were also seen in the case of genes involved in DNA damage response and repair, inflammation, oxidative stress response, and metal homeostasis. These results suggest that chronic low-dose arsenite exposure can lead to global hypomethylation. As an underlying mechanism, the consistent down-regulation of DNA methyltransferase genes could be excluded; alternatively, interactions at the protein level could play an important role. [ABSTRACT FROM AUTHOR]

Indole mechanism as an interspecies signal particle to adjust various physiological actions, like virulence, antimicrobial and acid resistance. This study was aimed to use partial purified indole extracted from uropathogenic E. coli and study the cytotoxic effect on some cancer cell lines (A375, HepG2, PC3) and comparable with normal cell line (WRL- 68). Serial dilutions of natural and synthetic standard indole were tested (400, 200, 100, 50, 25, 12.5, and 6.25 μg/mL). The results show a low cytotoxic effect for both natural and synthetic indoles in HepG2 and A375 cell lines as well as this degree of cytotoxicity was obviously appeared in normal cell line WRL-68 with no significant differences among them. While, both indoles effect was appeared high cytotoxic effect on PC3 cell line, this increasing has a significant difference with WRL-68. Thus, it can be suggesting that, this type of indole is not favorable for treatment of some types of cancer, and may has a specific biological activity against exact cancer cells. [ABSTRACT FROM AUTHOR]

There is an increasing incidence of liver cancer, which is a hazard for global health. The present study was designed to evaluate possible cytotoxic, genotoxic, apoptotic, oxidant and antioxidant effects of thymol on hepatocellular carcinoma (HepG2) cell line. The cytotoxic effect of thymol on HepG2 cell line was determined by XTT test. We also used the HUVEC cell line to show whether thymol damages healthy cells. Oxidative stress level was determined with Total Oxidant Status (TOS) and Total Antioxidant Status (TAS) measurement kits. Apoptosis of cells was detected in flow cytometry with Annexin V apoptosis kit. Apoptotic gene expressions were analyzed by real-time PCR. Genotoxicity was determined by comet assay, which measures DNA damage. The thymol IC50 dose was found to be 11 μM on HepG2 cell line. This dose had no lethal effect on the healthy HUVEC cell line. While thymol significantly decreased the TOS level, it increased the TAS level significantly in HepG2 cells compared to control. Thymol significantly induced apoptosis in HepG2 cells (apoptosis rate in control group 1%, in thymol group 21%). Thymol did not alter the gene expressions of bax, bcl-2, and casp3, all of which are associated with apoptosis. Statistically significant change in favor of genotoxicity was observed in tail length measurements. Our results suggest that thymol decreases oxidative stress in HepG2 cell line, but it induces apoptosis and genotoxicity. [ABSTRACT FROM AUTHOR]

Cisplatin is a classic anticancer drug widely used as a reference drug to test new metal complex drug candidates. We found an unexpected diversity in cisplatin-related cytotoxicity values, expressed as IC50 (the half-maximal inhibitory concentration) in tumour cell lines, such as MCF-7, HepG2 and HeLa. We reviewed the data published from 2018 to 2022. A total of 41 articles based on 56 in vitro experiments met our eligibility criteria. Using a meta-analysis based on a random effect model, we evaluated the cytotoxicity of cisplatin (IC50) after 48- or 72-h cell exposure. We found large differences between studies using a particular cell line. According to the random effect model, the 95% confidence intervals for IC50 were extremely wide. The heterogeneity of cisplatin IC50, as measured by the I2 index for all cancer cell lines, was over 99.7% at culture times of 48 or 72 h. Therefore, the variability between studies is due to experimental heterogeneity rather than chance. Despite the higher IC50 values after 48 h than after 72 h, the heterogeneity between the two culture periods did not differ significantly. This indicates that the duration of cultivation is not the main cause of heterogeneity. Therefore, the available data is diverse and not useful as a reference. We discuss possible reasons for the IC50 heterogeneity and advise researchers to conduct preliminary testing before starting experiments and not to solely rely on the published data. We hope that this systematic meta-analysis will provide valuable information for researchers searching for new cancer drugs using cisplatin as a reference drug. [ABSTRACT FROM AUTHOR]

CYP2C and CYP3A cytochromes are induced by a variety of compounds and affect the pharmacokinetics and pharmacodynamics of a large number of drugs. Currently, the possibility of using copper coordination compounds in antitumor therapy is being actively studied. Evaluation of potential interactions between new molecules and P450 cytochromes is necessary at an early stage of drug design.The aim. To study the modulating effect of Cu(II) complexes with enamine and tetrazole derivatives on CYP2C9, CYP2C19 and CYP3A4 and their cytotoxic and antiproliferative properties on normal human lung fibroblasts MRC-5 and a 3D model of hepatocellular carcinoma HepG2.Materials and methods. Cytotoxic and antiproliferative activities of copper(II) complexes – [CuL2] (1), [Cu2(bipy)2(PT)4] (2), [Cu2(phen)2(PT)4] (3), {[Cu(phen)(MT)2]∙H2O}n (4) (L – anion of 2-anilinomethylidene-5,5-dimethylcyclohexane-1,3-dione; PT – 5-phenyltetrazolate anion; MT – 5-methyltetrazolate anion; bipy – 2,2’-bipyridine; phen – 1,10-phenanthroline) – were examined in 2D and 3D models using fluorescence-based phenotypic screening. The modulating effect on CYP2C9, CYP2C19 and CYP3A4 was studied using fluorescence-based targeted screening. The results of CYP3A4 expression were confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR).Results. Complex (1) increases the CYP3A4 expression and does not affect CYP2C9 and CYP2C19 expression. Complex (2) has no modulating effect on CYP2C and CYP3A. Complexes with 1,10-phenatrolin (3) and (4) induce CYP3A4, inhibit CYP2C9 and do not affect CYP2C19 expression. All compounds have a dose-dependent cytotoxic effect on HepG2 and MRC-5: the compound with 5-methyltetrazolate anion (4) has the same effect on cell lines, compounds with 5-phenyltetrazolate anion (2) and (3) have selective effect. Complexes with 1,10-phenatrolin are effective on both 2D and 3D models.Conclusion. The [Cu2(phen)2(FT)4] complex (3) can be used as a basis for creating an antitumor compound, but further modification of the structure is required to increase the selectivity to tumor cells.

Nanoscale devices offer a lot of potential in drug delivery because of their small size. The goal of this work was to increase the oral bioavailability of the anti-cancer hydrophilic drug as 5-fluorouracil (5-FU) by incorporating it into poly (D, L-lactide-co-glycolide) nanoparticles (PLGNPs) using the double emulsion process, 5-FU- PLGNPs nanoparticles were created. Various factors, such as drug, polymer, and stabilizer concentrations, were investigated for assembly in order to arrive at the most effective formulation of 5-FU-PLGNPs. PLGNPs had a drug encapsulation efficiency of 9.75 to 24.8%. The prepared nanoparticles had a spherical shape and an average size of 212.3–285 nm, as shown by TEM. The dispersion of the drug into the prepared PLGNPs was confirmed by XRPD and FTIR. The optimized nanoparticles (F225) had high encapsulation efficiency 24.8 ± 0.21%, low particles size 212.3 ± 48.2 nm with an appropriate PDI value of 0.448, and ZP of − 48.3 ± 2.7 mV. The molecular dispersion of the medication within the system was validated by thermal behavior studies (DSC). In vitro drug release from the best-selected formulations revealed a sustained release of nanoparticles, with slower release reported when lower PVA concentrations were utilized. Three 5-FU-PLGNPs formulations were tested for anticancer efficacy against cell cultures of HCT-116 (human colorectal carcinoma), MCF-7 (human breast carcinoma), and HepG2 (human hepatocellular carcinoma). The created formulations were examined for in vitro cytotoxic activity, revealing that they appeared to be promising effective anticancer formulations when compared to the positive controlled (doxorubicin). [ABSTRACT FROM AUTHOR]

Ionic liquids (ILs) are a potential solution to the general problem of low solubility, polymorphism and low bioavailability of active pharmaceutical ingredients (APIs). In this work, we report on the synthesis of three pharmaceutically active ILs (API-ILs) based on ibuprofen, one of the most commonly available over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs), with imidazolium cations ([C2C1Im][Ibu] and [C2(OH)C1Im][Ibu]) and a cholinium cation ([N1112(OH)][Ibu]). An upgrade to the aqueous solubility (water and biological simulated fluids) for the ibuprofen-based ILs relative to the ibuprofen’s neutral and salt form (sodium ibuprofen) was verified. The cytotoxic profiles of the synthesized API-ILs were characterized using two human cells lines, Caco-2 colon carcinoma cells and HepG-2 hepatocellular carcinoma cells, up to ibuprofen’s maximum plasma concentration (Cmax) without impairing their cytotoxicity response. Additionally, the EC50 in the Caco-2 cell line revealed similar results for both parent APIs and API-ILs. The biocompatibility of the ibuprofen-based ILs was also evaluated through a hemolytic activity assay, and the results showed that all the ILs were hemocompatible at concentrations higher than the ibuprofen Cmax. Moreover, the anti-inflammatory properties of the API-ILs were assessed through the inhibition of bovine serum albumin (BSA) denaturation and inhibition of cyclooxygenases (COX-1 and COX-2). The results showed that [C2C1Im][Ibu], [C2(OH)C1Im][Ibu] and [N1112(OH)][Ibu] maintained their anti-inflammatory response to ibuprofen, with improved selectivity towards COX-2, allowing the development of safer NSAIDs and the recognition of new avenues for selective COX-2 inhibitors in cancer chemotherapy and neurological diseases such as Alzheimer’s and Parkinson’s.

To develop the risk prediction technology for mixture toxicity, a reliable and extensive dataset of experimental results is required. However, most published literature only provides data on combinations containing two or three substances, resulting in a limited dataset for predicting the toxicity of complex mixtures. Complex mixtures may have different mode of actions (MoAs) due to their varied composition, posing difficulty in the prediction using conventional toxicity prediction models, such as the concentration addition (CA) and independent action (IA) models. The aim of this study was to generate an experimental dataset comprising complex mixtures. To identify the target complex mixtures, we referred to the findings of the HBM4EU project. We identified three groups of seven to ten components that were commonly detected together in human bodies, namely environmental phenols, perfluorinated compounds, and heavy metal compounds, assuming these chemicals to have different MoAs. In addition, a separate mixture was added consisting of seven organophosphate flame retardants (OPFRs), which may have similar chemical structures. All target substances were tested for cytotoxicity using HepG2 cell lines, and subsequently 50 different complex mixtures were randomly generated with equitoxic mixtures of EC10 levels. To determine the interaction effect, we calculated the model deviation ratio (MDR) by comparing the observed EC10 with the predicted EC10 from the CA model, then categorized three types of interactions: antagonism, additivity, and synergism. Dose–response curves and EC values were calculated for all complex mixtures. Out of 50 mixtures, none demonstrated synergism, while six mixtures exhibited an antagonistic effect. The remaining mixtures exhibited additivity with MDRs ranging from 0.50 to 1.34. Our experimental data have been formatted to and constructed for the database. They will be utilized for further research aimed at developing the combined CA/IA approaches to support mixture risk assessment.

Amongst all cancer types, liver cancer is the fourth leading cause of cancer mortality. It is frequently stated as hepatocellular carcinoma (HCC) and occurs in hepatocytes. Genetic alterations of hepatocytes such as Wnt/β-catenin and JAK / STAT signaling pathways play a key role for the development of the HCC. Currently, there are a few available treatments for HCC; such treatments include transplantation, surgical resections and anticancer drugs. Most of the anti-cancer drugs target the signaling pathways for achieving an effective treatment. However, these treatments have some undesirable side effects. Thus, there is a need for discovering alternative anti-cancer agents with no or lesser side effects. Plant constituents are promising anti-cancer agents. Cynara cornigera L. contains plenty of phenolic compounds including quercetin, apigenin, etc. This study aimed to analyze the anti-cancer property of the fractionated methanol extract of the flowers of C. cornigera. All the fractions obtained were analyzed to determine the cytotoxic activity on HepG2 cells. Two of the fractions containing polyphenolic compounds had a significant cytotoxic activity related to non-canonical Wnt11 signaling pathways on HepG2 cells. [ABSTRACT FROM AUTHOR]

In this study, we designed and synthesized novel 1,4-dialkoxynaphthalene-2-alkyl imidazolium salt (IMS) derivatives containing both 1,4-dialkoxynaphthalene and imidazole, which are well known as pharmacophores. The cytotoxicities of these newly synthesized IMS derivatives were investigated in order to explore the possibility of using them to develop anticancer drugs. It was found that some of the new IMS derivatives showed good cytotoxic activities. In addition, an initial, qualitative structure–activity relationship is presented on the basis of observations of activity changes corresponding to structural changes. [ABSTRACT FROM AUTHOR]

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Abstract Background Phytochemicals and plant extracts are showing promising anticancer potentials. In the current study, the volatile faction (essential oil) of Nigella sativa seeds was evaluated against some hepatocellular carcinoma (HCC). The essential oil was extracted and characterized by chromatographic techniques to reveal its chemical composition, especially thymoquinone. Then, the oil was fabricated in two nanoemulsion formulations (F1 and F2), which differ in their composition of surfactants. The cytotoxicity and apoptotic activities of the essential oil and its nanoemulsions were evaluated in vitro against HepG2 and Huh-7 cell lines. Normal WI-38 cell line was also included in that evaluation to study the selectivity and safety of the different formulations on normal cells. Results Gas chromatographic analysis indicated that the essential oil is composed mainly of p-cymene (40.0%), thymoquinone (31.2%) and trans-α-thujene (12.8%). Particle size of the nanoemulsions ranged between 9.4 and 119.7 nm depending on the type of surfactant used in the formulation process. The pure essential oil and its two nanoemulsions (F1 and F2) showed dose-dependent antiproliferative activity against both HCC cells. This activity reached its highest cell inhibition in the case of nanoemulsion (F2) where the proliferation percentage was only 21.9% and 9.2% against HepG2 and Huh-7 cells, respectively. The same nanoemulsion (F2) also showed the lowest IC50 values (55.7 and 35.5 µg/ml) against both HepG2 and Huh-7 cells, respectively, compared to 100 µg/ml for the reference drug Doxorubicin. Flow cytometric analysis also confirmed that nanoemulsion (F2) has the highest apoptotic activity compared to nanoemulsion (F1) and the pure unformulated essential oil. Genetic expressions of pro-apoptotic (Bax) and the anti-apoptotic (Bcl-2) gene markers evaluation revealed that nanoemulsion (F2) has better activity in upregulating (Bax) and down-regulate (Bcl-2) with the highest Bax/Bcl-2 ratio (69) was found against Huh-7 cells. All N. sativa nanoemulsions showed minimal cytotoxicity on the normal WI-38 cell, indicating wide safety margins due to selective properties. Conclusion Overall, the study revealed the potentials of N. sativa essential oil, after formulation in specially tailored nanoemulsion for application as potential adjuvant liver anticancer agent. Graphical Abstract

Ionic liquids (ILs) are a potential solution to the general problem of low solubility, polymorphism and low bioavailability of active pharmaceutical ingredients (APIs). In this work, we report on the synthesis of three pharmaceutically active ILs (API-ILs) based on ibuprofen, one of the most commonly available over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs), with imidazolium cations ([C2C1Im][Ibu] and [C2(OH)C1Im][Ibu]) and a cholinium cation ([N1112(OH)][Ibu]). An upgrade to the aqueous solubility (water and biological simulated fluids) for the ibuprofen-based ILs relative to the ibuprofen's neutral and salt form (sodium ibuprofen) was verified. The cytotoxic profiles of the synthesized API-ILs were characterized using two human cells lines, Caco-2 colon carcinoma cells and HepG-2 hepatocellular carcinoma cells, up to ibuprofen's maximum plasma concentration (Cmax) without impairing their cytotoxicity response. Additionally, the EC50 in the Caco-2 cell line revealed similar results for both parent APIs and API-ILs. The biocompatibility of the ibuprofen-based ILs was also evaluated through a hemolytic activity assay, and the results showed that all the ILs were hemocompatible at concentrations higher than the ibuprofen Cmax. Moreover, the anti-inflammatory properties of the API-ILs were assessed through the inhibition of bovine serum albumin (BSA) denaturation and inhibition of cyclooxygenases (COX-1 and COX-2). The results showed that [C2C1Im][Ibu], [C2(OH)C1Im][Ibu] and [N1112(OH)][Ibu] maintained their anti-inflammatory response to ibuprofen, with improved selectivity towards COX-2, allowing the development of safer NSAIDs and the recognition of new avenues for selective COX-2 inhibitors in cancer chemotherapy and neurological diseases such as Alzheimer's and Parkinson's. [ABSTRACT FROM AUTHOR]

Nanobiomaterials, or NBMs, have been used in medicine and bioimaging for decades, with wide-reaching applications ranging from their uses as carriers of genes and drugs, to acting as sensors and probes. When developing nanomedicine products, it is vitally important to evaluate their safety, ensuring that both biocompatibility and efficacy are achieved so their applications in these areas can be safe and effective. When discussing the safety of nanomedicine in general terms, it is foolish to make generalised statements due to the vast array of different manufactured nanomaterials, formulated from a multitude of different materials, in many shapes and sizes; therefore, NBM pre-clinical screening can be a significant challenge. Outside of their distribution in the various tissues, organs and cells in the body, a key area of interest is the impact of NBMs on the liver. A considerable issue for researchers today is accurately predicting human-specific liver toxicity prior to clinical trials, with hepatotoxicity not only the most cited reasons for withdrawal of approved drugs, but also a primary cause of attrition in pre-launched drug candidates. To date, no simple solution to adequately predict these adverse effects exists prior to entering human experimentation. The limitations of the current pre-clinical toolkit are believed to be one of the main reasons for this, with questions being raised on the relevance of animal models in pre-clinical assessment, and over the ability of conventional, simplified in vitro cell–based assays to adequately assess new drug candidates or NBMs. Common 2D cell cultures are unable to adequately represent the functions of 3D tissues and their complex cell–cell and cell–matrix interactions, as well as differences found in diffusion and transport conditions. Therefore, testing NBM toxicity in conventional 2D models may not be an accurate reflection of the actual toxicity these materials impart on the body. One such method of overcoming these issues is the use of 3D cultures, such as cell spheroids, to more accurately assess NBM-tissue interaction. In this study, we introduce a 3D hepatocellular carcinoma model cultured from HepG2 cells to assess both the cytotoxicity and viability observed following treatment with a variety of NBMs, namely a nanostructured lipid carrier (in the specific technical name = LipImage™ 815), a gold nanoparticle (AuNP) and a panel of polymeric (in the specific technical name = PACA) NBMs. This model is also in compliance with the 3Rs policy of reduction, refinement and replacement in animal experimentation [1], and meets the critical need for more advanced in vitro models for pre-clinical nanotoxicity assessment. Pipeline for the pre-clinical assessment of NBMs in liver spheroid model [ABSTRACT FROM AUTHOR]

In this study, 5-fluorouracil (5-FU) entrapped polycaprolactone nanoparticles (5-FU- PCNPs) have been prepared using double emulsion method. The different factors were examined for assembly to arrive at the best effective formulation of 5-FU-PCNPs formulation for 5-FU–PCNPs, as polymer concentration, stabilizer concentration. The encapsulation efficiency of PCNPs was in the range of 18.8–45.4%. The prepared nanoparticles showed the spherical shape having an average size of 183–675.5 nm, whereas TEM exhibited the prepared nanoparticles have a spherical shape. FTIR, XRPD, confirmed successful insertion of drug in prepared PCNPs. In vitro release of 5-FU from selected formulations showed sustained release from the nanoparticles where slower release was observed when lower PVA concentration was used. Anticancer activity was examined against cell culture for HCT-116 (human colorectal carcinoma), MCF-7(human breast adenocarcinoma), HepG2 (human hepatocellular carcinoma) and A549 (human lung carcinoma) for six formulations 5-FU–PCNPs nanoparticles. The in vitro cytotoxic activity of the prepared formulations was tested showing that these formulations appeared as promising active anticancer formulations. [ABSTRACT FROM AUTHOR]

The knowledge about the effect of hydrotalcites (HTlcs), largely used in pharmaceutics, on non-malignant cell lines is limited. The effect of MgAl-HTlc-and ZnAl-HTlc- (NO3−/Cl−/CO32−) on the cell viability of HaCat, fibroblasts and HepG2 was studied by MTT assay. Cells were incubated either with HTlc suspensions in the culture media and with the supernatant obtained from the suspension being centrifuged. MgAl-HTlcs suspensions resulted in being cytotoxic. As SEM and TEM analyses showed the presence of sub-micrometric particles in all the MgAl-HTlc examined, it could be hypothesized that this fraction can be internalized into cells reducing the viability. MgAl-HTlc-NO3 is the most cytotoxic probably due to the additional effect of NO3− anions. ZnAl-HTlcs are cytotoxic, especially for HaCat and HepG2 cells (viability <60% at all the concentrations assayed). The effect is attributable both to the sub-micrometric fraction (identified by TEM) and to the high Zn2+ levels found in the culture medium by ICP-OES analysis, suggesting that ZnAl-HTlcs are less stable than MgAl-HTlc in the used media. The obtained results suggest that it is very important to perform ad hoc studies in order to evaluate HTlc safety before to be introduced in a formulation. [ABSTRACT FROM AUTHOR]

Polyamine (PA) catabolism is often reduced in cancer cells. The activation of this metabolic pathway produces cytotoxic substances that might cause apoptosis in cancer cells. Chemical compounds able to restore the level of PA catabolism in tumors could become potential antineoplastic agents. The search for activators of PA catabolism among bicyclononan-9-ones is a promising strategy for drug development. The aim of the study was to evaluate the biological activity of new 3,7-diazabicyclo[3.3.1]nonan-9-one derivatives that have antiproliferative properties by accelerating PA catabolism. Eight bispidine derivatives were synthetized and demonstrated the ability to activate PA catabolism in regenerating rat liver homogenates. However, only three of them demonstrated a potent ability to decrease the viability of cancer cells in the MTT assay. Compounds 4c and 4e could induce apoptosis more effectively in cancer HepG2 cells rather than in normal WI-38 fibroblasts. The lead compound 4e could significantly enhance cancer cell death, but not the death of normal cells if PAs were added to the cell culture media. Thus, the bispidine derivative 4e 3-(3-methoxypropyl)-7-[3-(1H-piperazin-1-yl)ethyl]-3,7-diazabicyclo[3.3.1]nonane could become a potential anticancer drug substance whose mechanism relies on the induction of PA catabolism in cancer cells. [ABSTRACT FROM AUTHOR]

Resistance to glyphosate herbicide has initiated usage of combined application of herbicides as a weed control measure. Imazethapyr-based herbicides associated with glyphosate herbicide seem to be an alternative to suppress weed resistance. The aim of this study was to examine the adverse effects of Glyphosate Atanor 48® (ATN) and Imazethapyr Plus Nortox® (IMZT) formulations in both single forms and mixtures using HepG2 cells and zebrafish early-life stages models. Data demonstrated cytotoxicity due to exposure to ATN, IMZT for both models, as follows: (1) ATN (0.5 mg/L), IMZT (5 mg/L), and M3 (0.05 mg/L ATN + 5 mg/L IMZT) increased cytotoxicity by disturbing the mitochondrial activity of HepG2 cells 24 hr after exposure; (2) ATN and IMZT (5 mg/L), and M3 (0.05 mg/L ATN + 5 mg/L IMZT) also decreased the integrity of the membrane of HepG2 cells after 24 hr incubation; (3) only ATN and IMZT (5 mg/L) in their single forms diminished the mitochondrial potential of zebrafish; (4) ATN (single form) at 0.5 mg/L induced apoptosis in zebrafish larvae. In conclusion, these herbicides in their single forms appeared to produce greater cytotoxicity to HepG2 cells and zebrafish compared to the herbicide mixtures. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (GNPs) have shown great potential in diagnostic and therapeutic applications in diseases, such as cancer. Despite GNP versatility, there is conflicting data regarding the toxicity of their overall functionalization chemistry for improved biocompatibility. This study aimed to determine the possible genotoxic effects of functionalized GNPs in Human hepatocellular carcinoma (HepG2) cells. GNPs were synthesized and biofunctionalized with seven common molecules used for biomedical applications. These ligands were bovine serum albumin (BSA), poly(sodium 4-styrene sulfonate) (PSSNA), trisodium citrate (citrate), mercaptoundecanoic acid (MUA), glutathione (GSH), polyvinylpyrrolidone (PVP), and polyethylene glycol (PEG). Before in vitro genotoxicity assessment, inductively coupled plasma mass spectrometry was used to determine GNP cellular internalization quantitatively, followed by cell-based assays; WST-1 to find IC 30 and ApoPercentage for apoptotic induction time-points. The effect of the GNPs on cell growth in real-time was determined by using xCELLigence, followed by a comet assay for genotoxicity determination. The HepG2 cells experienced genotoxicity for all GNP ligands; however, they were able to initiate repair mechanisms and recover DNA damage, except for two functionalization chemistries. [ABSTRACT FROM AUTHOR]

Erythrodiol (EO) is a pentacyclic triterpenic alcohol found in olive tree leaves and olive oil, and it has important effects on the health properties and quality of olive oil. In this study, we characterized the cytotoxic effects of EO on human hepatocarcinoma (HepG2) cells by studying changes in cell viability, reactive oxygen species (ROS) production, antioxidant defense systems, and the proteome. The results reveal that EO markedly decreased HepG2 cell viability without changing ROS levels. The concentrations of glutathione and NADPH were significantly reduced, with selective changes in the activity of several antioxidant enzymes: glutathione peroxidase, glutathione reductase, glucose 6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. Proteomic data reveal that EO led to the complete elimination or decreased abundance of 41 and 3 proteins, respectively, and the abundance of 29 proteins increased. The results of functional enrichment analysis show that important metabolic processes and the nuclear transport of mature mRNA were impaired, whereas AMP biosynthesis and cell cycle G2/M phase transition were induced. The transcription factors and miRNAs involved in this response were also identified. These potent antiproliferative effects make EO a good candidate for the further analysis of its hepatic antitumor effects in in vivo studies [ABSTRACT FROM AUTHOR]

Background: Cousinia Cass. is one of the most diverse genus of Asteraceae family. According to previous studies some Cousinia species showed significant cytotoxic activity. Purpose: In this study, we aimed to investigate the cytotoxic activity and phytochemical profile of four Cousinia species (C.davisiana Hub.-Mor., C.foliosa Boiss. & Balansa, C.ramosissima DC, C.stenocephala Boiss). Methods: The cytotoxic activity was investigated with SRB method against HepG2 (human hepatocellular carcinoma) cell line. The quantitative and qualitative determination of compounds were carried out by LC-MS/MS. Results: In a result, C. davisiana methanol extract (CD) and ethyl acetate sub-extract (CDE) showed more cytotoxic activity with 150 and 89 µg/ml IC50 values, respectively. The mass spectrums revealed the presence of 15 compounds in CD methanol extract and 9 compounds in active CDE sub-extract. According to quantitative analyses the highest contents of all compounds were detected in CD extract. Conclusion: Moreover, this study on inhibitory activity of CD extract and CDE sub-extract suggests detailed investigation for cytotoxic activity.

Background: Phytochemicals and plant extracts are showing promising anticancer potentials. In the current study, the volatile faction (essential oil) of Nigella sativa seeds was evaluated against some hepatocellular carcinoma (HCC). The essential oil was extracted and characterized by chromatographic techniques to reveal its chemical composition, especially thymoquinone. Then, the oil was fabricated in two nanoemulsion formulations (F1 and F2), which differ in their composition of surfactants. The cytotoxicity and apoptotic activities of the essential oil and its nanoemulsions were evaluated in vitro against HepG2 and Huh-7 cell lines. Normal WI-38 cell line was also included in that evaluation to study the selectivity and safety of the different formulations on normal cells. Results: Gas chromatographic analysis indicated that the essential oil is composed mainly of p-cymene (40.0%), thymoquinone (31.2%) and trans-α-thujene (12.8%). Particle size of the nanoemulsions ranged between 9.4 and 119.7 nm depending on the type of surfactant used in the formulation process. The pure essential oil and its two nanoemulsions (F1 and F2) showed dose-dependent antiproliferative activity against both HCC cells. This activity reached its highest cell inhibition in the case of nanoemulsion (F2) where the proliferation percentage was only 21.9% and 9.2% against HepG2 and Huh-7 cells, respectively. The same nanoemulsion (F2) also showed the lowest IC50 values (55.7 and 35.5 µg/ml) against both HepG2 and Huh-7 cells, respectively, compared to 100 µg/ml for the reference drug Doxorubicin. Flow cytometric analysis also confirmed that nanoemulsion (F2) has the highest apoptotic activity compared to nanoemulsion (F1) and the pure unformulated essential oil. Genetic expressions of pro-apoptotic (Bax) and the anti-apoptotic (Bcl-2) gene markers evaluation revealed that nanoemulsion (F2) has better activity in upregulating (Bax) and down-regulate (Bcl-2) with the highest Bax/Bcl-2 ratio (69) was found against Huh-7 cells. All N. sativa nanoemulsions showed minimal cytotoxicity on the normal WI-38 cell, indicating wide safety margins due to selective properties. Conclusion: Overall, the study revealed the potentials of N. sativa essential oil, after formulation in specially tailored nanoemulsion for application as potential adjuvant liver anticancer agent. [ABSTRACT FROM AUTHOR]

Intake of synthetic cannabinoids (SC), one of the largest classes of new psychoactive substances, was reported to be associated with acute liver damage but information about their hepatotoxic potential is limited. The current study aimed to analyze the hepatotoxicity including the metabolism-related impact of JWH-200, A-796260, and 5F-EMB-PINACA in HepG2 cells allowing a tentative assessment of different SC subclasses. A formerly adopted high-content screening assay (HCSA) was optimized using a fully automated epifluorescence microscope. Metabolism-mediated effects in the HCSA were additionally investigated using the broad CYP inhibitor 1-aminobenzotriazole. Furthermore, phase I metabolites and isozymes involved were identified by in vitro assays and liquid chromatography–high-resolution tandem mass spectrometry. A strong cytotoxic potential was observed for the naphthoylindole SC JWH-200 and the tetramethylcyclopropanoylindole compound A-796260, whereas the indazole carboxamide SC 5F-EMB-PINACA showed moderate effects. Numerous metabolites, which can serve as analytical targets in urine screening procedures, were identified in pooled human liver microsomes. Most abundant metabolites of JWH-200 were formed by N-dealkylation, oxidative morpholine cleavage, and oxidative morpholine opening. In case of A-796260, most abundant metabolites included an oxidative morpholine cleavage, oxidative morpholine opening, hydroxylation, and dihydroxylation followed by dehydrogenation. Most abundant 5F-EMB-PINACA metabolites were generated by ester hydrolysis plus additional steps such as oxidative defluorination and hydroxylation. To conclude, the data showed that a hepatotoxicity of the investigated SC cannot be excluded, that metabolism seems to play a minor role in the observed effects, and that the extensive phase I metabolism is mediated by several isozymes making interaction unlikely. [ABSTRACT FROM AUTHOR]

The continuous emergence of new psychoactive substances (NPS) attracted a great deal of attention within recent years. Lately, the two hallucinogenic NPS 1cP-LSD and 4-AcO-DET have appeared on the global market. Knowledge about their metabolism to identify potential metabolic targets for analysis and their cytotoxic properties is lacking. The aim of this work was thus to study their in vitro and in vivo metabolism in pooled human liver S9 fraction (pHLS9) and in zebrafish larvae (ZL) by means of liquid chromatography-high-resolution tandem mass spectrometry. Monooxygenases involved in the initial metabolic steps were elucidated using recombinant human isozymes. Investigations on their cytotoxicity were performed on the human hepatoma cell line HepG2 using a multiparametric, fluorescence-based high-content screening assay. This included measurement of CYP-enzyme mediated effects by means of the unspecific CYP inhibitor 1-aminbenzotriazole (ABT). Several phase I metabolites of both compounds and two phase II metabolites of 4-AcO-DET were produced in vitro and in vivo. After microinjection of 1cP-LSD into the caudal vein of ZL, three out of seven metabolites formed in pHLS9 were also detected in ZL. Twelve 4-AcO-DET metabolites were identified in ZL after exposure via immersion bath and five of them were found in pHLS9 incubations. Notably, unique metabolites of 4-AcO-DET were only produced by ZL, whereas 1cP-LSD specific metabolites were found both in ZL and in pHLS9. No toxic effects were observed for 1cP-LSD and 4-AcO-DET in HepG2 cells, however, two parameters were altered in incubations containing 4-AcO-DET together with ABT compared with incubations without ABT but in concentrations far above expected in vivo concentration. Further investigations should be done with other hepatic cell lines expressing higher levels of CYP enzymes. • Metabolism of two hallucinogens was compared using the pHLS9 and zebrafish larvae model. • Identification of unique metabolic targets possible for both NPS using the zebrafish larvae model. • Few CYP isoenzymes involved in metabolic steps of 1cP-LSD may be relevant if co-consumed with other drugs (of abuse). • No cytotoxicity in hepatic cells (HepG2) observed for both compounds using a high-content screening assay approach. • Metabolism-based cytotoxicity of 4-AcO-DET cannot be excluded. [ABSTRACT FROM AUTHOR]

There is very limited knowledge about in vitro hepatotoxicity of permethrin concerning dose and duration even though humans and nontargeted beings are exposed. In this study, three different doses of permethrin (1 uM, 10 uM, 100 uM) were administered in three different time periods (24, 48, 72 h) and cell viability (WST-1 and Trypan blue test), lipid peroxidation (high performance lipid chromatography), and antioxidant (SOD-1, SOD-2 and GPx-1) gene expression levels (real time PCR) were evaluated. The LC50 dose of permethrin was calculated as 1111 μM. Significant decrease in cell viability was detected in every time period except at the lowest dose (P

Plants have natural products which use to possess antiproliferative potential against many cancers. In the present study, six isolated fractions (ethyl acetate, petroleum ether, chloroform, n-butanol, ethanol and aqueous) from Solanum nigrum were evaluated for their cytotoxic effect on different cell lines. Hepatic carcinoma cell line (HepG2), cervical cancer cell line (HeLa) and baby hamster kidney (BHK) used as normal non-cancerous cells were evaluated for cytotoxicity against isolated fractions. Cell viability assay was performed to evaluate the cytotoxicity of all fractions on different cell lines followed by the lactate dehydrogenase and vascular endothelial growth factor assays of most active fraction among all screened for cytotoxic analysis. HPLC analysis of most active fractions against cytotoxicity was performed to check the biological activity of compounds. Results displayed the potent cytotoxic activity of ethyl acetate fraction of S. nigrum against HepG2 cells with IC 50 value of 7.89 μg/ml. Other fractions exhibited potent anticancer activity against HepG2 cells followed by HeLa cells. Fractions in our study showed no cytotoxicity in BHK cells. Cytotoxic activity observed in our current study exposed high antiproliferative potential and activity of ethyl acetate fraction against HepG2 cells. The results demonstrated that S. nigrum fractions exhibited anticancer activity against hepatic and cervical cancer cell lines with non-toxic effect in normal cells. These results reveal significant potential of S. nigrum for the therapeutic of cancers across the globe in future. [ABSTRACT FROM AUTHOR]

The pulsed plasma-chemical method was used to obtain zinc oxide-contthe morphology and histograms of the particle aining silicon and titanium oxide nanocomposites (ZnOx-SiO2 and ZnOx-TiO2). To realize the method, a TEA-500 pulsed electron accelerator (Tomsk, Russia) was used. Zinc oxide (ZnO) nanopowder was obtained using the electrospark method. The morphology and phase composition of the synthesized nanopowders were determined using transmission electron microscopy (TEM) and X-ray diffraction (XRD) methods. The cytotoxicity of ZnO, ZnOx-SiO2, and ZnOx-TiO2 nanomaterials on HepG2 and 3T3-L1 adhesive cell lines was studied using thiazolyl blue tetrazolium bromide (MTT; Sigma). It was found that the size of the synthesized particles was in the range of 40–150 nm. The phase composition of ZnO, ZnOx-SiO2, and ZnOx-TiO2 nanomaterials was presented by several crystal structures. The dominant crystal lattice was ZnO with a hexagonal lattice for the ZnO sample, Zn (hexagonal lattice) for the ZnOx-SiO2 sample, and anatase for the ZnOx-TiO2 sample. The morphology of the ZnO, ZnOx-SiO2, and ZnOx-TiO2 nanoparticles was diverse. The cytotoxicity of ZnOx-SiO2 composite nanomaterials was much lower than that of the ZnO nanoparticles. The effect of increasing the viability of cells under the influence of low doses of ZnOx-TiO2 composite nanomaterials was revealed. These research results may present useful information for specialists involved in the development and application of functional nanocomposites. [ABSTRACT FROM AUTHOR]

There is grave necessity to counter the menace of drug-resistant biofilms of pathogens using nanomaterials. Moreover, we need to produce nanoparticles (NPs) using inexpensive clean biological approaches that demonstrate broad-spectrum inhibition of microbial biofilms and cytotoxicity against HepG2 cell lines. In the current research work, titanium dioxide (TiO2) NPs were fabricated through an environmentally friendly green process using the root extract of Withania somnifera as the stabilizing and reducing agent to examine its antibiofilm and anticancer potential. Further, X-ray diffraction (XRD), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), transmission electron micrograph (TEM), energy-dispersive X-ray spectroscopy (EDS), dynamic light scattering (DLS), thermogravimetric analysis (TGA), and Brunauer-Emmett-Teller (BET) techniques were used for determining the crystallinity, functional groups involved, shape, size, thermal behavior, surface area, and porosity measurement, respectively, of the synthesized TiO2 NPs. Antimicrobial potential of the TiO2 NPs was determined by evaluating the minimum inhibitory concentration (MIC) against Escherichia coli, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, Listeria monocytogenes, Serratia marcescens, and Candida albicans. Furthermore, at levels below the MIC (0.5 × MIC), TiO2 NPs demonstrated significant inhibition of biofilm formation (43–71%) and mature biofilms (24–64%) in all test pathogens. Cell death due to enhanced reactive oxygen species (ROS) production could be responsible for the impaired biofilm production in TiO2 NP–treated pathogens. The synthesized NPs induced considerable reduction in the viability of HepG2 in vitro and could prove effective in controlling liver cancer. In summary, the green synthesized TiO2 NPs demonstrate multifarious biological properties and could be used as an anti-infective agent to treat biofilm-based infections and cancer.

In the current study a new technique between the plasma physics, nanoparticle and Biotechnology,structured (ZnSe) prepared by cold plasma technique using atmospheric pressure plasmajet system, Znse NPs were prepared from selenium nitrate and zinc metal sheets to reduce selenium toxicity. The structural and optical properties were characterized by X-ray diffraction (XRD) and absorbance measurements of ZnSe green NPs. The liver cancer cell line (hepG2) was exposed to the ZnSe nanoparticles, and The percentage of cytotoxicity was suppressed after 24, and48 from exposure, induced cytotoxicity is found to be 70.3% in hepG2 after exposed 48h ZnSe green nanoparticle, and the maximum cytotoxicity of the normal cell line (REF) was also examined 42.62% when exposure ZnSe nanoparticles and 16.6% when exposure ZnSe green nanoparticles. [ABSTRACT FROM AUTHOR]

In this study, a well-organized, simplistic, and biological route of AgNPs (AgNPs) was synthesized using shrimp shell extracted chitin as reducing, capping and stabilizing factor under the optimized conditions. Also, the anticancer potential of synthesized biogenic AgNPs was evaluated against human hepatocarcinoma (HepG2) cells. Ultraviolet visible spectroscopy (UV–Vis spec) study indicated that the development of AgNPs present in the colloidal solution was single peak at 446 nm. FTIR results showed a strong chemical interaction between the chitin and biogenic AgNPs; whereas, XRD studies confirmed AgNPs presence in the composites. The SEM TEM analytical studies confirmed the synthesized AgNPs had a spherical shape crystalline structure with size ranges from 17 to 49 nm; EDX study also confirmed the percentage of weight and atomic elements available in the colloidal mixture. Furthermore, the synthesized AgNPs showed significant cytotoxic effect on the HepG2 cells with an IC 50 value shown at 57 ± 1.5 μg/ml. The apoptotic and necrotic cell death effects of AgNPs were also confirmed by flow cytometry. The upregulated apoptotic related proteins Bax, cytochrome-c, caspase-3, caspase-9, PARP and downregulated anti-apoptotic related proteins Bcl-2 and Bcl-xl in cancer cells, confirmed the anticancer potential of AgNPs. These findings suggest that the AgNPs possess significant anticancer activity against HepG2 cells which could play major role in the therapeutic drug development to treat cancer in future. [ABSTRACT FROM AUTHOR]

Pleurotus eryngii, a type of edible mushroom that exhibit various pharmacological properties, including antioxidant and anticancer effects. In the present study, extracted β-glucan from the P eryngii was tested as an antioxidant and anti-tumor factor. β-glucan was extracted and analyzed by HPLC and FT-IR. Analytical results showed more than 90% similarity in chemical structure and purity. Potential antioxidant activity of β-glucan was examined using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and compared with ascorbic acid. β-glucan confirmed a potential scavenging activity. The anticancer activity of the β-glucan was assessed using different concentrations (6.25 to 400 µg mL-1) on MCF-7 and HepG2 cell lines. P eryngii β-glucan exerted a dose-dependent reduction in MCF-7 and HepG2 cell viability with an IC50 of 280.00 and 539.5 µg mL-1, respectively. At the same time, no significant effect was recorded on normal cell line WRL 68. The obtained results are expected that could be used to develop P eryngii β-glucan as an antitumor drug. [ABSTRACT FROM AUTHOR]

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There is grave necessity to counter the menace of drug-resistant biofilms of pathogens using nanomaterials. Moreover, we need to produce nanoparticles (NPs) using inexpensive clean biological approaches that demonstrate broad-spectrum inhibition of microbial biofilms and cytotoxicity against HepG2 cell lines. In the current research work, titanium dioxide (TiO2) NPs were fabricated through an environmentally friendly green process using the root extract of Withania somnifera as the stabilizing and reducing agent to examine its antibiofilm and anticancer potential. Further, X-ray diffraction (XRD), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), transmission electron micrograph (TEM), energy-dispersive X-ray spectroscopy (EDS), dynamic light scattering (DLS), thermogravimetric analysis (TGA), and Brunauer-Emmett-Teller (BET) techniques were used for determining the crystallinity, functional groups involved, shape, size, thermal behavior, surface area, and porosity measurement, respectively, of the synthesized TiO2 NPs. Antimicrobial potential of the TiO2 NPs was determined by evaluating the minimum inhibitory concentration (MIC) against Escherichia coli , Pseudomonas aeruginosa , methicillin-resistant Staphylococcus aureus , Listeria monocytogenes , Serratia marcescens , and Candida albicans. Furthermore, at levels below the MIC (0.5 × MIC), TiO2 NPs demonstrated significant inhibition of biofilm formation (43–71%) and mature biofilms (24–64%) in all test pathogens. Cell death due to enhanced reactive oxygen species (ROS) production could be responsible for the impaired biofilm production in TiO2 NP–treated pathogens. The synthesized NPs induced considerable reduction in the viability of HepG2 in vitro and could prove effective in controlling liver cancer. In summary, the green synthesized TiO2 NPs demonstrate multifarious biological properties and could be used as an anti-infective agent to treat biofilm-based infections and cancer. [ABSTRACT FROM AUTHOR]

Study on phytochemistry, antioxidant and cytotoxicity properties of Hydnophytum formicarum leaves against HepG2 and HeLa cancer cell lines were described. The leaves were dried in a freeze dryer and successively extracted using hexane and methanol. Phytochemicals screening revealed the presence of several compounds including phenols/tannins, flavonoids, glycosides and steroids. Antioxidant property was examined using DPPH free radical scavenging assay. Methanol extract exhibited higher antioxidant activity (IC50=0.4 mg/mL) compared to hexane extract (IC50=2 mg/mL). However, the cytotoxicity result by MTT assay showed only methanol extract exhibited moderate cytotoxic activity against HeLa cell line (IC50=25 mg/mL). Both extracts showed no cytotoxic activity against HepG2 cell line. This study suggests that H. formicarum leaves have potency as a new source of antioxidant and anticancer agents, especially for cervical cancer. However, further study to separate the bioactive compounds of the extract and by using different cell lines is required to discover the potential of H. formicarum leaves as antioxidant and anticancer agents. [ABSTRACT FROM AUTHOR]

We aimed to assess the antitumor activity of Orobanche crenata methanolic extract and evaluate its cytotoxic effect on different cancer cell lines to develop an effective natural anticancer drug. Components of O. crenata methanolic extract were analyzed using gas chromatography–mass spectrometry. The extract's antioxidant activity was assessed by 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power procedures and cytotoxicity of the extract was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase assays. Caspase-3 activity was also estimated. O. crenata methanolic extract shows powerful antioxidant activity. The extract inhibited the propagation of human hepatocellular carcinoma (HepG2), human prostate cancer (PC3), human breast adenocarcinoma (MCF-7), and human colon carcinoma (HCT-116) in a dose-dependent manner. O. crenata– treated cells displayed obvious morphological structures distinctive of apoptosis. MTT assay exposed that the extract presented prevention of cell persistence in a dose-dependent means and revealed extremely cytotoxic activity against HepG2, PC3, MCF-7, and HCT-116 with 50% inhibitory concentration values 30.3, 111, 89.6, and 28.6 µg/mL, respectively, after 24 h of incubation. In addition, treatment of HCT-116 with various concentrations of the extract caused the release of lactate dehydrogenase and induction of caspase-3 activity in a dose-dependent way. In conclusion, our findings suggested that the O. crenata extract possesses potent antioxidant, cytotoxic activity, and anticancer properties which are possibly due to the principal bioactive phytochemical composites existing in this plant. These results can be used to develop new drugs for cancer treatment. [ABSTRACT FROM AUTHOR]

In the present study of 4,5-diphenyl-1-((tetrahydrofuran-2-yl)methyl)-2-(3,4,5-trichlorophenyl)- ¹H-imidazole 1 was synthesized. The synthesized imidazole compound 1 has been characterized by FTIR, ¹H, 13C NMR and ESI-Mass spectral studies. Molecular docking is also performed in order to explain the over expression of estrogen receptor in 70% of liver cancer. The imidazole scaffold is a privileged scaffold for exploration of anticancer agents. The objective of the present study is to evaluate the anticancer activity of imidazole 1 in human liver cancer cell lines HepG2. [ABSTRACT FROM AUTHOR]

Chromatographic investigation of the aerial parts of the Rhazya stricta (Apocynaceae) resulted in the isolation of two new monoterpene indole alkaloids, 6-nor-antirhine-N1-methyl (1) and razyamide (2), along with six known compounds, eburenine (3), epi-rhazyaminine (4), rhazizine (5), 20-epi-sitsirikine (6), antirhine (7), and 16-epi-stemmadenine-N-oxide (8). The chemical structures were established by various spectroscopic experiments. Compounds 1–8 exhibited cytotoxic effects against three cancer cells with IC50 values ranging between 5.1 ± 0.10 and 93.2 ± 9.73 µM against MCF-7; 5.1 ± 0.28 and 290.2 ± 7.50 µM against HepG2, and 3.1 ± 0.17 and 55.7 ± 4.29 µM against HeLa cells. Compound 2 showed the most potent cytotoxic effect against all cancer cell lines (MCF-7, HepG2 and HeLa with IC50 values = 5.1 ± 0.10, 5.1 ± 0.28, and 3.1 ± 0.17 µM, respectively). Furthermore, compound 2 revealed a significant increase in the apoptotic cell population of MCF-7, HepG2, and HeLa cells, with 31.4 ± 0.2%, 29.2 ± 0.5%, and 34.9 ± 0.6%, respectively. Compound 2 decreased the percentage of the phagocytic pathway on HepG2 cells by 15.0 ± 0.1%. These findings can explain the antiproliferative effect of compound 2.