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

  • Parmidafathiroshan ,1,*
    1. Islamic Azad University, Central Tehran Branch


  • Introduction: Breast cancer is the most common cancer worldwide and a major cause of cancer-related death. Current treatments, including chemotherapy and surgery, have significant limitations and side effects. MCF-7 and MDA-MB-231 breast cancer cell lines differ in their hormone receptor status, making them useful models for studying breast cancer therapies. Actinomycetes are important producers of biologically active secondary metabolites, including antibiotics and antitumor compounds, and have contributed to the development of many drugs. Due to their potential as a source of new anticancer agents, this study investigated the antitumor activity of Streptomyces violaceochromogenes extract against MCF-7 and MDA-MB-231 breast cancer cell lines.
  • Methods: Streptomyces violaceochromogenes was cultured and its secondary metabolites were extracted and analyzed by LC–MS. The anticancer activity of the extract was evaluated in MCF-7 and MDA-MB-231 breast cancer cells using the MTT assay to determine cell viability and cytotoxicity. Flow cytometry was performed to investigate apoptosis and cell-cycle changes. The expression of apoptosis-related genes was evaluated using real-time PCR. In the animal study, the antitumor effects of the extract were assessed in a breast cancer model, followed by histopathological examination of tumor tissues to evaluate treatment-related morphological changes.
  • Results: The results demonstrated that the secondary-metabolite extract obtained from Streptomyces violaceochromogenes exhibited significant anticancer activity against the breast cancer cell lines MCF-7 and MDA-MB-231. The MTT assay showed a concentration-dependent reduction in cell viability following treatment with the bacterial extract, indicating its cytotoxic effects on breast cancer cells. Flow cytometry analysis further demonstrated an increase in the proportion of apoptotic cells after treatment, suggesting that the extract induces programmed cell death. Changes in cell-cycle distribution were also observed in treated cells compared with untreated controls. The results of real-time PCR showed significant changes in the expression of genes associated with the apoptotic pathway, supporting the involvement of apoptosis in the anticancer effects of the extract. LC-MS analysis identified several secondary metabolites and bioactive compounds in the extract, which may contribute to its observed cytotoxic and antitumor properties. In the in vivo study, administration of the extract resulted in a reduction in tumor growth compared with the control group. The histopathological examination of tumor tissues revealed treatment-associated morphological changes and increased tissue damage in the treated groups. These findings were consistent with the results obtained from the in vitro experiments. Overall, the combined MTT, flow cytometry, real-time PCR, LC-MS, animal, and histopathological analyses demonstrated that Streptomyces violaceochromogenes produces bioactive secondary metabolites with potential antitumor effects against breast cancer models.
  • Conclusion: The findings of this study demonstrated that the secondary-metabolite extract of Streptomyces violaceochromogenes possesses promising anticancer and antitumor properties against breast cancer models. The extract reduced the viability of MCF-7 and MDA-MB-231 cells, while flow cytometry indicated the induction of apoptosis and cell-cycle alterations. Changes in the expression of apoptosis-related genes, detected by real-time PCR, further supported the involvement of apoptotic pathways in the observed cytotoxic effects. LC-MS analysis revealed the presence of several bioactive secondary metabolites that may contribute to the anticancer activity of the extract. Furthermore, the in vivo and histopathological findings supported its inhibitory effects on tumor growth and confirmed treatment-associated changes in tumor tissues. Overall, S. violaceochromogenes represents a promising source of bioactive compounds for further investigation in breast cancer research and potential anticancer drug development.
  • Keywords: In vivo; MCF-7; apoptosis; Streptomyces violaceochromogenes; Caspase 8; Caspase 3/7.0

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