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In this study, the anticancer effect of Melittin was demonstrated through its antiproliferative and proapoptotic effects on HT-29 cells, as well as its ability to reverse multidrug resistance. Melittin directly affects the death receptor-dependent apoptotic pathway via increase of the Fas receptor protein expression, Caspase 8 gene expression and activity of Caspase 8. Results of decreased Caspase 9 gene and protein expression, and multi-fold increased expression of Bcl-2 gene suggest that mitochondria and the inner apoptotic pathway are not involved in the execution of Melittin induced apoptosis, as well as redox regulation of apoptosis based on decreased concentration of superoxide anion radicals and no effect glutathione levels. Specially significance of this work are results on ability of Melittin to modulate the metabolism and export system in cancer cells. Based on the increased expression of all the investigated genes related to the biotransformation process, it can be assumed that CYP1A1, CYP1B1, GSTP1 and MRP2 are involved in metabolism of Melittin in HT-29 cells. P-glycoprotein is associated with the occurrence of resistance in anticancer therapy, so its reduced gene and protein expression by Melittin represents significant result in terms of possible therapeutic application and examination. [ABSTRACT FROM AUTHOR]

Breast cancer is the most diagnosed invasive cancer and the second leading cause of cancer in women. Standard medicinal protocol for treatment of this disease implies surgery and use of chemotherapeutic drugs. It is known that these drugs are associated with resistance, cancer relapse, and numerous side effects. Researchers give great importance to natural bioactive compounds because of their conformed health beneficial effects. Ocimum minimum L. is a well-known plant in folk medicine for treating various diseases and conditions, whit a large specter of pharmaceutical activities. The aim of this study is to evaluate anticancer properties and impact on fatty acid synthesis process under the influence of O. minimum L. flowers in triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) and normal fetal fibroblasts (MRC-5). The impact of O. minimum L. on fatty acid synthesis process in breast cancer cells has been evaluated through cytotoxic activity by MTT assay, pro-apoptotic activity by AO/EB staining, concentrations of redox status parameters (O2.-, lipid peroxidation, GSH) by colorimetric methods. The expression of genes involved in fatty acid synthesis (ACLY, FASN, MAGL, HIF-1α) were determined by the qPCR method, while the protein expression (FASN) was analyzed by immunocytochemistry. Based on the obtained results, synergic action between bioactive compounds identified from O. minimum L. showed cytotoxic, proapoptotic, and prooxidant effects on breast cancer cell lines, as well as suppression of genes and protein (FASN) involved in fatty acid synthesis process. This plant showed significant pharmacological effects whit potential use as nutritional supplement in anticancer therapy. [ABSTRACT FROM AUTHOR]

The paper investigates anticancer effects of methanol extracts of invasive plant species Robinia pseudoacacia L. (RpE) and Amorpha fruticosa L. (AfE) on breast cancer MDA-MB-231 and healthy MRC-5 cells. The anticancer activity was evaluated through examination of cytotoxic effects, anti-invasive potential and impact on redox status in comparative analysis using their chemical composition. According to the IC50 values, the investigated plants had no significant cytotoxic effects either on healthy cell line MRC-5 or on MDA-MB-231 cancer cells, but they showed great anti-invasive potential by suppressing all investigated parameters of tumor invasion and metastases (Matrix Metalloproteinases (MMP), protein concentration and MMP-9, C-X-C Motif Chemokine Ligand 12 (CXCL-12), Vascular Endothelial Growth Factor (VEGF-A) and Hypoxia-Inducible Factor (HIF-1α) gene expression) in MDA-MB-231 cells. Based on their remarkable anti-invasive potential, RpE and AfE are suitable for use as potential supplements in anticancer therapy or as nutritional food supplements. [ABSTRACT FROM AUTHOR]

Breast cancer as most often women's cancer is the second cause of mortality worldwide. Research interest increased in testing non-standard drugs to suppress breast cancer progression and become significant supplements in anticancer therapy. The anti-obesity drug Orlistat showed significant ability for modulation of cancer cell metabolism via antiproliferative, proapoptotic, antiangiogenic, antimetastatic, and hypolipidemic effects. The anticancer potential of Orlistat was evaluated by cytotoxicity (MTT assay), type of cell death (AO/EB double staining), determination of redox status parameters (superoxide, hydrogen peroxide, lipid peroxidation, reduced glutathione), and total lipid levels with colorimetric methods, as well on angiogenesis-related (VEGF, MMP-9, CXCR4/CXCL12) and fatty acid synthesis-related (ACLY, ACC, FASN) parameters on gene and protein levels (immunocytochemistry and qPCR). Based on obtained results Orlistat induces significant cytotoxic, proapoptotic, and anti-angiogenic effects in MDA-MB-231, MDA-MB-468 and MCF-7 breast cancer cells, without significant cytotoxic effects on normal MRC-5 cells. It decreased total lipid levels and changed redox status parameters and cancer cell metabolism via suppression of genes and proteins involved and fatty acid synthesis. Based on showed, Orlistat may be an important supplement in antiangiogenic therapy against breast cancer with no side effects on normal cells, making it a good candidate for future clinical trials. [ABSTRACT FROM AUTHOR]

This study evaluated the potential of antitumor activity of snake venom from Vipera ammodytes and L-amino acid oxidase from Crotalus adamanteus on different colorectal cancer cell lines through determination of cytotoxic activity by MTT assay, pro-apoptotic activity by acridine orange/ethidium bromide staining, and concentrations of redox status parameters (superoxide, reduced glutathione, lipid peroxidation) by colorimetric methods. The expression of genes involved in the biotransformation process and metabolite efflux was determined by qPCR method, while protein expression of glutathione synthetase and P-glycoprotein were analysed by immunocytochemistry. The analysis of cell death shows that snake venom dominantly leads cells to necrosis. Induction of apoptosis by L-amino acid oxidase was in correlation with oxidative disbalance in cancer cells. Gene expression profile of membrane transporters and CYP genes were different in each cell line and in correlation with their sensitivity of treatment. Our results show that L-amino acid oxidase from snake venom is a potent cytotoxic substance with pronounced pro-apoptotic activity. The inhibition of P-glycoprotein suggests that L-amino acid oxidase is a good substance for furter research of antitumor effect, with unexpressed potential for occurrence of drug resistance in vitro. [Display omitted] • LAAO from Crotalus adamanteus venom is a proapoptotic agent. • The mechanism of their proapoptotic effect was mediated by changes in redox status. • LAAO change expression of genes involved in biotransformation processes. • Our in vitro results do not indicate the possibility of resistance occurrence. [ABSTRACT FROM AUTHOR]