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Given the development of drug-resistant cancer cells, designing alternative approaches for cancer treatment seems essential. In this study, we evaluated the anti-tumor effects of nisin A and Newcastle disease virus (NDV) on triple-negative MDA-MB-231 cell line. The MDA-MB-231 cell line was separately and in combination subjected to the different concentrations of a Veroadapted NDV (JF820294.1) and nisin A. The oncolytic effects of these treatments were analyzed by different cytotoxic and apoptosis techniques including trypan blue staining, MTT assay, acridine orange (EB/AO) staining, colony assay and flow cytometry over time. Nisin A at doses of more than 20.00 μg mL-1 could represent the anti-viral effects and interfere with the oncolytic activity of NDV. Moreover, the analyses indicated that the anti-proliferative and cytotoxic features of combination therapy were stronger than those of individual NDV groups. However, the most apoptotic effect was seen in NDV experimental groups. Taken together, the results from cytotoxicity tests, flow cytometry and colony assay showed that either of the oncolytic agents had significant effects at low concentrations 72 hr post-treatment. Thereby, they had the potential to be used as new approaches in cancer treatment. [ABSTRACT FROM AUTHOR]

Abnormal vasculature is one of the most conspicuous traits of tumor tissue, largely contributing to tumor immune evasion. The deregulation mainly arises from the potentiated pro-angiogenic factors secretion and can also target immune cells' biological events, such as migration and activation. Owing to this fact, angiogenesis blockade therapy was established to fight cancer by eliminating the nutrient and oxygen supply to the malignant cells by impairing the vascular network. Given the dominant role of vascular-endothelium growth factor (VEGF) in the angiogenesis process, the well-known anti-angiogenic agents mainly depend on the targeting of its actions. However, cancer cells mainly show resistance to anti-angiogenic agents by several mechanisms, and also potentiated local invasiveness and also distant metastasis have been observed following their administration. Herein, we will focus on clinical developments of angiogenesis blockade therapy, more particular, in combination with other conventional treatments, such as immunotherapy, chemoradiotherapy, targeted therapy, and also cancer vaccines. 64SciJHJrfLYaKT285oK4U Video abstract [ABSTRACT FROM AUTHOR]

Development of drug resistance has considerably limited the efficacy of cancer treatments, including chemotherapy and targeted therapies. Hence, understanding the molecular mechanisms underpinning the innate or the acquired resistance to these therapies is critical to improve drug efficiency and clinical outcomes. Several studies have implicated microRNAs (miRNA) in this process. MiRNAs repress gene expression by specific binding to complementary sequences in the 3' region of target messenger RNAs (mRNAs), followed by target mRNA degradation or blocked translation. By targeting molecules specific to a particular pathway within tumor cells, the new generation of cancer treatment strategies has shown significant advantages over conventional chemotherapy. However, the long‐term efficacy of targeted therapies often remains poor, because tumor cells develop resistance to such therapeutics. Targeted therapies often involve monoclonal antibodies (mAbs), such as those blocking the ErB/HER tyrosine kinases, epidermal growth factor receptor (cetuximab) and HER2 (trastuzumab), and those inhibiting vascular endothelial growth factor receptor signaling (e.g., bevacizumab). Even though these are among the most used agents in tumor medicine, clinical response to these drugs is reduced due to the emergence of drug resistance as a result of toxic effects in the tumor microenvironment. Research on different types of human cancers has revealed that aberrant expression of miRNAs promotes resistance to the aforementioned drugs. In this study, we review the mechanisms of tumor cell resistance to mAb therapies and the role of miRNAs therein. Emerging treatment strategies combine therapies using innovative miRNA mimics or antagonizers with conventional approaches to maximize outcomes of patients with cancer. This literature review discuss the role of microRNAs in cancer cell resistance to targeted therapies. In addition, it discuss the molecular mechanisms underlying the development of therapeutic drug resistance based on basic evidence and clinical applications. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of Tetraphenylporphyrin and H2T(4-SO2Cl)PP. • Conjugation of functionalized porphyrin to albumin-metronidazole nanoparticles. • In vitro radiation/photodynamic therapy. Breast cancer is the second leading cause of cancer death in women after lung cancer. In the context of cancer therapy, chemotherapy regarded as the most common method of treatment, but besides this beneficial modality, radiation therapy (RT) is used as a supplementary or palliative treatments. In this regard, we aimed at preparing albumin- Tetraphenylporphyrin -metronidazole nanosystem (BSA-Met- H2T(4-SO2)PP NPs) as an effective photo/radiosensitizer along with RT to tackle breast cancer. Accordingly, the synthesized nanosystems were analyzed by various characterization techniques such as dynamic light scattering (DLS), fourier transform infrared spectroscopy (FT-IR), UV–vis, and proton nuclear magnetic resonance (1HNMR), also transmission electron microscopy (TEM) technique was used to determine the morphology and size of fabricated nanosystems. Moreover, the biosafety of developed nanosystems were ascertained using LD 50 and hemolysis assay. Based on DLS measurements the average size and polydispersity index of fabricated nanosystems were about 190 nm and 0.36, respectively. The BSA-Met-H2T(4-SO2)PP NPs showed pH-dependent drug release behavior. The results showed that the drug loading (DL) for metronidazole and Tetraphenylporphyrin were 3.406% and 13.586%, respectively. Both hemolysis and LD 50 confirmed the biosafety of the BSA-Met-H2T(4-SO2)PP NPs. Finally, MTT assay revealed that the prepared nanoparticles exhibited great anti-cancer activity upon radiation and light against 4 T1 cancer cells. Overall, our findings suggest that PPHN-MET NPs may be promising candidates for the effective radiation/or light-induced cancer therapy. [ABSTRACT FROM AUTHOR]

Immune cells are recruited into the tumor microenvironment and regulate anti- and pro-tumor signals. MicroRNAs (miRNAs) markedly control the immune system responses in cancer development. miRNAs that affect the immune system could be interesting targets for immunomodulation against cancer, either through the activation of effector cells or through the down-regulation of regulatory cells. Bioinformatic calculations can predict the immune system and miRNA interactions. In this review, we discuss the most recent studies about miRNA as the main regulator of recruitment and the activation of the immune system in the tumor microenvironment and finally we propose several miRNAs that could serve as therapeutic molecules in the immunotherapy of cancer. [ABSTRACT FROM AUTHOR]

MicroRNAs’ expression profiles have recently gained major attention as far as cancer research is concerned. MicroRNAs are able to inhibit target gene expression via binding to the 3′ UTR of target mRNA, resulting in target mRNA cleavage or translation inhibition. MicroRNAs play significant parts in a myriad of biological processes; studies have proven, on the other hand, that aberrant microRNA expression is, more often than not, associated with the growth and progression of cancers. MicroRNAs could act as oncogenes (oncomir) or tumor suppressors and can also be utilized as biomarkers for diagnosis, prognosis, and cancer therapy. Recent studies have shown that such herbal extracts as Shikonin, Sinomenium acutum, curcumin, Olea europaea, ginseng, and Coptidis Rhizoma could alter microRNA expression profiles through inhibiting cancer cell development, activating the apoptosis pathway, or increasing the efficacy of conventional cancer therapeutics. Such findings patently suggest that the novel specific targeting of microRNAs by herbal extracts could complete the restriction of tumors by killing the cancerous cells so as to recover survival results in patients diagnosed with malignancies. In this review, we summarized the current research about microRNA biogenesis, microRNAs in cancer, herbal compounds with anti-cancer effects and novel strategies for employing herbal extracts in order to target microRNAs for a better treatment of patients diagnosed with cancer. [ABSTRACT FROM AUTHOR]

Introduction Medical plants have been intensively studied as a source of antitumor compounds. In the present study, we determine the effect of Scrophularia oxysepala on triggering apoptosis and diminishing growth, size and weight of the tumor in the allograft model of Balb/c mice. Material & methods The cytotoxic effects of Scrophularia oxysepala extract on 4T1 cells were studied using MTT (3-[4,5-dimethyl-2-thiazolyl]-2, 5 diphenyl tetrazolium bromide) assay and Trypan blue staining. DNA fragmentation assay was done for apoptosis detection. After the establishment of tumor in Balb/c mice, two groups of mice were received the extract at two doses of 50 and 100 mg/kg respectively using intraperitoneal injection once every two days for 28 days. In order to assess the induction of apoptosis in cancer cells, the TUNEL assay was carried out in tumoral tissues. Moreover, the Ki67 test was used to evaluate tumor proliferation. Results According to the findings, the Scrophularia oxysepala extract inhibited cell growth. In vivo results showed that tumor size in mice treated with the extract was significantly reduced. The weight of tumor mass in treated mice after resection was less than the control group. According to the TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) assay results, the herbal extract induced apoptosis in tumoral cells. Ki67 test also demonstrated that administration of the extract suppressed the growth of tumor cells. Conclusion Our data well approved the anti-proliferative effect of Scrophularia oxysepala extract, and clearly showed that, the plant extract can decrease the growth of breast cancer cells in tumor mass. Thus it may represent an ideal therapeutic tool for breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: HMGI-C (High Mobility Group protein Isoform I-C) protein is a member of the high-mobility group AT-hook (HMGA) family of small non-histone chromosomal protein that can modulate transcription of an ample number of genes. Genome-wide studies revealed up regulation of the HMGI-C gene in many human cancers. We suggested that HMGI-C might play a critical role in the progression and migration of various tumors. However, the exact role of HMGI-C in breast adenocarcinoma has not been cleared. Methods:The cells were transfected with siRNAs using transfection reagent. Relative HMGI-C mRNA and protein levels were measured by quantitative real-time PCR and Western blotting, respectively. The cytotoxic effects of HMGI-C siRNA, Paclitaxel alone and combination on breast adenocarcinoma cells were determined using MTT assay. The migration after treatment by HMGI-C siRNA, Paclitaxel alone and combination were detected by wound-healing respectively. Results: HMGI-C siRNA significantly reduced both mRNA and protein expression levels in a 48 hours after transfection and dose dependent manner. We observed that the knockdown of HMGI-C led to the significant reduced cell viability and inhibited cells migration in MDA-MB-468 cells in vitro. Conclusion: These results propose that HMGI-C silencing and Paclitaxel treatment alone can inhibit the proliferation and migration significantly, furthermore, synergic effect of HMGI-C siRNA and Paclitaxel showed higher inhibition compared to mono treatment. Taken together, HMGI-C could be used as a promising therapeutic agent in the treatment of human breast adenocarcinoma. Therefore HMGI-C siRNA may be an effective adjuvant in human breast adenocarcinoma. [ABSTRACT FROM AUTHOR]

The transcription factor high mobility group protein A2 (HMGA2) plays an important role in the pathogenesis of some cancers including breast cancer. Polyamidoamine dendrimer generation 4 is a kind of highly branched polymeric nanoparticle with surface charge and highest density peripheral groups that allow ligands or therapeutic agents to attach it, thereby facilitating target delivery. Here, methotrexate (MTX)- modified polyamidoamine dendrimer generation 4 (G4) (G4/MTX) was generated to deliver specific small interface RNA (siRNA) for suppressing HMGA2 expression and the consequent effects on folate receptor (FR) expressing human breast cancer cell lines (MCF-7, MDA-MB-231). We observed that HMGA2 siRNA was electrostatically adsorbed on the surface of the G4/MTX nanocarrier for constructing a G4/MTX-siRNA nano-complex which was verified by changing the final particle size and zeta potential. The release of MTX and siRNA from synthesized nanocomplexes was found in a time- and pH-dependent manner. We know that MTX targets FR. Interestingly, G4/MTX-siRNA demonstrates significant cellular internalization and gene silencing efficacy when compared to the control. Besides, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay demonstrated selective cell cytotoxicity depending on the FR expressing in a dose-dependent manner. The gene silencing and protein downregulation of HMGA2 by G4/MTX-siRNA was observed and could significantly induce cell apoptosis in MCF-7 and MDA-MB-231 cancer cells compared to the control group. Based on the findings, we suggest that the newly developed G4/MTX-siRNA nano-complex may be a promising strategy to increase apoptosis induction through HMGA2 suppression as a therapeutic target in human breast cancer. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is considered one of the leading types of cancer in the world. CD133, as a cancer stem cell marker, has a pivotal role in the development of drug resistance, migration, and stemness properties of CRC cells. This study was designed to check the combined effect of CD133 siRNA and Oxaliplatin on proliferation, migration, apoptosis, and stemness properties of CRC cells in the HT-29 cell line. MTT assay was performed to define the combined effect of CD133 siRNA and Oxaliplatin on the viability of HT-29 cells, and it showed that the combination of CD133 siRNA and Oxaliplatin could reduce the IC50 of this drug from 32.85 to 19.75 nmol. In order to figure out the effect of this combination therapy on CD133 expression at the gene and protein level, qRT-PCR and western blot were exploited, respectively. The results demonstrated that the silencing of CD133 could reduce the relative expression of this marker to about 0.00001 compared to the control group and reduce the protein level to 0.01. The ability of cell migration was tested by wound healing assay as well. Also, colony formation and sphere formation were conducted to assess the stemness properties in the combination group. Flow cytometry was conducted to investigate the apoptosis (15%), cell cycle (about 10% arresting in G0-G1 phase), and surface expression of CD133 in different groups (from 39.3% in the control group to 2.41 in the combination group). Finally, the expression of migration-, and stemness-associated genes were measured by qRT-PCR. We indicated that silencing of CD133 reduces the migration and stemness properties of colorectal cancerous cells. This suppression makes HT-29 cells more sensitive to Oxaliplatin and reduces the effective dose of this chemical drug. Therefore, the suppression of CD133 in combination with Oxaliplatin treatment might be a promising therapeutic approach in the treatment of colorectal cancer. [Display omitted] • Silencing of CD133 makes HT-29 cells more sensitive to Oxaliplatin. • Silencing of CD133 reduces migration and stemness properties. • CD133 silencing decreases metastasis and stemness related genes expression. • CD133 silencing in combination with Oxaliplatin induces apoptosis. [ABSTRACT FROM AUTHOR]

[Display omitted] • BSA coated Pt nanoparticles was applied as both radiosensitizer and drug carrier. • In terms of morphology, nanoparticles appeared to be homogenous and monodispersed. • The results disclosed that designed nanoplatform due to the presence of Pt and BSA had ability to kill cancer cells effectively. Bovine serum albumin (BSA) coated platinum (Pt) nanoparticles (Pt@BSA NPs) were synthesized, followed by the conjugation of an anticancer drug (MTX) with the aim of chemoradiation therapy. The physical and chemical properties of Pt@BSA-MTX were evaluated by DLS, FESEM, STEM, UV–Vis and XRD. A release study was performed in the presence and absence of the proteinase K enzyme. In terms of morphology, nanoparticles appeared to be monodispersed and spherical. The size of nanoparticles was 7.4 ± 1.4 nm. Release behavior of Pt@BSA-MTX depended significantly on enzyme presence which accelerated and promoted the release of MTX. The improved chemoradiation was demonstrated in vitro using MTT, colony formation and apoptosis assays on mouse breast carcinoma cells (4T1). It was concluded that the combination of a nanoradiosensitizer with a chemotherapeutic agent resulted in superior anticancer activity after X-ray exposure. [ABSTRACT FROM AUTHOR]

BACH1 (BTB and CNC homology 1, basic leucine zipper transcription factor 1) is a transcriptional factor and a member of cap ‘n’ collar (CNC) and basic region leucine zipper factor family. In contrast to other bZIP family members, BACH1 appeared as a comparatively specific transcription factor. It acts as transcription regulator and is recognized as a recently hypoxia regulator and functions as an inducible repressor for the HO-1 gene in many human cell types in response to stress oxidative. In regard to studies lately, although, BACH1 has been related to the regulation of oxidative stress and heme oxidation, it has never been linked to invasion and metastasis. Recent studies have showed that BACH1 is involved in bone metastasis of breast cancer by up-regulating vital metastatic genes like CXCR4 and MMP1. This newly discovered aspect of BACH1 gene provides new insight into cancer progression study and stands on its master regulator role in metastasis process, raising the possibility of considering it as a potential target for cancer therapy. [ABSTRACT FROM AUTHOR]