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This study synthesized gold nanoparticles (AuNPs) using a facile microwave-assisted chemical route and evaluated them as potential anticancer candidates against breast and colon cancer cell lines. Numerous spectral characterization tools were used to study the optical properties, structure, and morphology of the prepared AuNPs. UV-Vis spectroscopy showed a characteristic peak at 517 nm, which confirms the formation of AuNPs. The crystalline structure of NPs was studied by X-ray diffraction, and the NPs’ shape and size were calculated with Field emission transmission electron microscopy. The synthesized AuNPs were found to be uniform in size in the range of 2–6 nm. A variety of biological tests, including MTT, scratch, real time polymerase chain reaction (RT-PCR), and comet assays were adopted to assess the anticancer potential of these AuNPs in the studied cancer cell models. The findings suggested a cell-dependent cytotoxicity of AuNPs. Different cell viability of 40.3 and 66.4% were obtained for MCF-7 and HCT-116, respectively, at 5 µg/mL of AuNPs. The scratch assay showed AuNPs impede cell migration in a concentration-dependent manner in the MCF-7 cell line. On the other hand, real-time polymerase chain reaction (RT-PCR) of apoptotic (p53, Bax, and caspase-3) and anti-apoptotic (BCl-2) genes revealed upregulation and downregulation of these genes, respectively, probably leading to its cytotoxicity. At 5 µg/mL concentration of AuNPs, reactive oxygen species (ROS) production was found to be increased by 26.4 and 42.7%, respectively, in MCF-7 and HCT-116 cells. Similarly, comet assay demonstrated AuNPs induced DNA damage in the studied cancer cell lines. These findings suggest that the observed anticancer efficacy of AuNPs was driven by ROS generation. The synthesized AuNPs appeared to be a promising therapeutic against cancer cells. However, our in vitro data need to be confirmed and validated in ex vivo and in vivo models so that this NP can be further exploited for human use.

In the present study, pumpkin seed extract was used to synthesize copper oxide nanoparticles (CuO NPs) along with evaluating its anticancer activity using different molecular biology tools in the human colorectal cancer cell line (HCT-116). Morphological and structural properties of the biogenically synthesized CuO NPs were characterized by UV-visible spectrophotometry (UV-vis), energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). For estimating the anticancer efficacy, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity, morphological alteration, reactive oxygen species (ROS) formation, and alterations in the mitochondrial membrane potential (MMP) were determined. SEM and TEM data revealed the formation of spherical nanoparticles possessing an average size of 20 nm. The CuO NPs showed 50% inhibitory concentration (IC50) at 25 µg/mL against the HCT-116 cell line. The treatment with IC50 concentration of CuO NPs showed significant shrinking, detachment, membrane blebbing, and shape distortion of cancer cells. Similarly, the IC50 dose of CuO NPs showed significantly early apoptosis in cancer cells compared to late apoptosis. The cancer cell line also showed a dose-dependent increase and decrease in ROS formation and MMP, respectively. The results obtained through various assays indicated significant anticancer efficacy of biogenically synthesized CuO NPs. Thus, further studies are recommended to validate our results using ex vivo and in vivo models.

The green approach of synthesizing nanoparticles is an efficient, cost-effective, environmentally friendly, and rapid technique in which plant sources act as capping/stabilizing and reducing agents. The current study aimed to investigate the anticancer potential of biosynthesized Cu4O3 NPs against the human ovarian teratocarcinoma cell line (PA-1). Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and selected area electron diffraction (SAED) were used to predict the size and morphology of the biosynthesized nanoparticles. The SEM image revealed a 200 nm size of Cu4O3 NPs; however, TEM data showed the spherical shape of the Cu4O3 NPs in the range of ≤ 100 nm. A range of biological evaluations, such as cytotoxicity assay, morphological alteration, induction of apoptosis by three different staining techniques (AO/EB dual staining, DAPI, and PI staining), ROS production, and alteration in mitochondrial membrane potential were performed. We observed a dose-dependent cytotoxicity of Cu4O3 NPs in the PA-1 cell line with an IC50 dose of 9.5 µg/ml. Furthermore, Cu4O3 NP treatment induced apoptosis, which was confirmed by all three adopted staining techniques while inducing ROS production and modulating mitochondrial membrane potential. Our findings highlight the anticancer potential of Cu4O3 NPs against the studied cell line, which needs to be further explored because of its cost-effectiveness and eco-friendly nature. [ABSTRACT FROM AUTHOR]

Cu4O3 is the least explored copper oxide, and its nanoformulation is anticipated to have important therapeutic potential especially against cancer. The current study aimed to biosynthesize Cu4O3 nanoparticles (NPs) using an aqueous extract of pumpkin seeds and evaluate its antiproliferative efficacy against cervical cells after screening on different cancer cell lines. The obtained NPs were characterized by different spectroscopic analyses, such as UV‐vis, thermogravimetric, energy dispersive X‐ray, and Fourier‐transform infrared spectroscopy (FTIR). In addition, high‐resolution transmission electron microscopes (HR‐TEM) were used to observe the morphology of the biosynthesized NPs. The UV‐vis spectra showed a peak at around 332 nm, confirming the formation of Cu4O3 NPs. Moreover, FTIR and TAG analyses identified the presence of various bioactive phytoconstituents that might have worked as capping and stabilization agents and comparative stable NPs at very high temperatures, respectively. The HR‐TEM data showed the spherical shape of Cu4O3 NPs in the range of 100 nm. The Cu4O3 NPs was screened on three different cancer cell lines viz., Hela, MDA‐MB‐231, and HCT‐116 using cytotoxicity (MTT) reduction assay. In addition, Vero was taken as a normal epithelial (control) cell. The high responsive cell line in terms of least IC50 was further assessed for its anticancer potential using a battery of biological tests, including morphological alterations, induction of apoptosis/ROS generation, regulation of mitochondrial membrane potential (MMP), and suppression of cell adhesion/migration. Vero cells (control) showed a slight decline in % cell viability even at the highest tested Cu4O3 NPs concentration. However, all the studied cancer cells viz., MDA‐MB‐231, HCT 116, and HeLa cells showed a dose‐dependent decline in cell viability after the treatment with Cu4O3 NPs with a calculated IC50 value of 10, 11, and 7.2 µg/mL, respectively. Based on the above data, Hela cells were chosen for further studies, that showed induction of apoptosis from 3.5 to 9‐folds by three different staining techniques acridine orange/ethidium bromide (AO/EB), 4′,6‐diamidino‐2‐phenylindole (DAPI), and propidium iodide (PI). The enhanced production of reactive oxygen species (>3.5‐fold), modulation in MMP, and suppression of cell adhesion/migration were observed in the cells treated with Cu4O3 NPs. The current study obtained the significant antiproliferative potential of Cu4O3 NPs against the cervical cancer cell line, which needs to be confirmed further in a suitable in vivo model. Based on our results, we also recommend the green‐based, eco‐friendly, and cost‐effective alternative method for synthesizing novel nanoformulation. Significance Statement: Cu4O3 NPs was biosynthesized using pumpkin seeds aqueous extract.The biogenic Cu4O3 NPs was found to be spherical and ~100 nm size.A dose‐dependent cytotoxicity with a IC50 value of 7.2 µg/mL was observed against Hela cells.Induction of apoptosis up to 9‐fold was observed using different staining techniques.The enhanced production of reactive oxygen species, modulation in mitochondrial membrane potential, and suppression of cell adhesion/migration were observed in the cells treated with Cu4O3 NPs. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD), the most predominant cause of dementia, has evolved tremendously with an escalating frequency, mainly affecting the elderly population. An effective means of delaying, preventing, or treating AD is yet to be achieved. The failure rate of dementia drug trials has been relatively higher than in other disease-related clinical trials. Hence, multi-targeted therapeutic approaches are gaining attention in pharmacological developments. Aims: As an extension of our earlier reports, we have performed docking and molecular dynamic (MD) simulation studies for the same 13 potential ligands against beta-site APP cleaving enzyme 1 (BACE-1) and c-secretase as a therapeutic target for AD. The In-silico screening of these ligands as potential inhibitors of BACE-1 and c-secretase was performed using AutoDock enabled PyRx v-0.8. The protein-ligand interactions were analyzed in Discovery Studio 2020 (BIOVIA). The stability of the most promising ligand against BACE-1 and c-secretase was evaluated by MD simulation using Desmond-2018 (Schrodinger, LLC, NY, USA). Results: The computational screening revealed that the docking energy values for each of the ligands against both the target enzymes were in the range of -7.0 to -10.1 kcal/mol. Among the 13 ligands, 8 (55E, 6Z2, 6Z5, BRW, F1B, GVP, IQ6, and X37) showed binding energies of ≦-8 kcal/mol against BACE-1 and c-secretase. For the selected enzyme targets, BACE-1 and c-secretase, 6Z5 displayed the lowest binding energy of -10.1 and -9.8 kcal/mol, respectively. The MD simulation study confirmed the stability of BACE-6Z5 and c-secretase-6Z5 complexes and highlighted the formation of a stable complex between 6Z5 and target enzymes. Conclusion: The virtual screening, molecular docking, and molecular dynamics simulation studies revealed the potential of these multi-enzyme targeted ligands. Among the studied ligands, 6Z5 seems to have the best binding potential and forms a stable complex with BACE-1 and c-secretase. We recommend the synthesis of 6Z5 for future in-vitro and in-vivo studies. [ABSTRACT FROM AUTHOR]