Antitumor Effects of Phenols and Peptides from Streptomyces violaceochromogenes M12 on Breast Cancer in Mice

Breast cancer, the most common cancer globally, has prompted research into alternative treatments due to potential harm from conventional methods. Bacterial agents, particularly actinomycetes, are being explored as a source of biologically active secondary metabolites with antitumor properties and other pharmaceutical applications. This study investigated the antitumor activity of Streptomyces violaceochromogenes strain M12 extract against breast cancer. The extract's cytotoxic effect was evaluated on MCF-7, MDA-MB-231, and MCF-10A cell lines using MTT assay, real-time PCR, and flow cytometry. The MCF7 cell line showed the lowest survival rate at 48 hours (IC50: 24.58 μg/ml), while the extract demonstrated selective cytotoxicity against MCF-10A cells. Treatment of MCF-7 cells resulted in increased apoptotic cells. Gene expression analysis revealed reduced Bax and caspase 9 levels, while caspase 8 expression and caspase 3/7 activity increased, suggesting an extrinsic apoptosis pathway. In vivo studies using Balb/c mice showed reduced mitoses, nuclear pleomorphism, and tumor angiogenesis in tumor tissue. LC-MS analysis identified 11 metabolites, mostly phenolic and peptid compounds in the extract, potentially contributing to its apoptotic effect. These findings indicate that the S. violaceochromogenes M12 extract effectively induces MCF-7 cell death and may serve as a promising alternative treatment for breast cancer.