Targeting Mitochondrial-Nuclear Apoptotic Signaling Pathways, Metabolic Pathways and Reversal of Doxorubicin (DOX) Cell Resistance in MCF-۷ and MDA‑MB-۲۳۱ Cancer Cell Lines by Sambucus Nigra (SNA)

Background: The study aimed to assess the effect of anti-tumor and anti-proliferative properties of Sambucus nigra (SNA) on MCF-۷ and MDA-MB-۲۳۱ breast tumor cell lines. Methods: The cytotoxicity of SNA was assessed based on dose/time by the MTT assay. Also, the influence of SNA on apoptotic pathways, cellular and metabolic resistance in these cell lines was examined by real-time PCR, lipid peroxidase was measured by malondialdehyde (MDA) and the effect of apoptosis and necrosis was determined by flow cytometry. Results: Our data showed that DOX, SNA, and DOX + SNA treatment induced the expression of p۵۳, Bax, Bcl-۲, Caspase-۳, and ۸ levels involved in the apoptotic pathways. ATP binding cassette subfamily B member ۴ (ABCB۴) gene expression was decreased in MDA‑MB-۲۳۱ breast cancer cells compared to MCF-۷. Also, we observed that DOX, SNA, and DOX + SNA treatment induced expression of Monocarboxylate transporters (MCTs) metabolic pathways such as MCT۱ and MCT۴. Conclusion: Overall, the outcomes of this investigation show that the combination of SNA-Doxorubicin (DOX) in different groups of these cancer cells, especially in the MDA‑MB-۲۳۱ cell lines synergistically intensified the induction of apoptosis in them. SNA enhances the anti-cancer effects of DOX to induce cellular apoptosis, alter metabolic pathways, and reduce cellular resistance. The research highlights the promising use of SNA as a chemosensitizer in the chemotherapy.

کلیدواژه ها:

Breast cancer ، Doxorubicin ، Drug resistance ، Sambucus nigra