Open AccessTargeting Mitochondrial-Nuclear Apoptotic Signaling Pathways, Metabolic Pathways and Reversal of Doxorubicin (DOX) Cell Resistance in MCF-7 and MDA‑MB-231 Cancer Cell Lines by Sambucus Nigra (SNA)
Author(s) -
Ali Ghanbari,
Shiva Roshankhah,
Mohammad Reza Salahshoor,
Cyrus Jalili,
Mojtaba Esmaeli
Publication year - 2022
Publication title -
archives of breast cancer
Language(s) - English
Resource type - Journals
eISSN - 2383-0433
pISSN - 2383-0425
DOI - 10.32768/abc.20229183-95
Subject(s) - apoptosis , mcf 7 , doxorubicin , mtt assay , cancer cell , viability assay , biology , cancer research , cancer , cell culture , pharmacology , chemistry , biochemistry , chemotherapy , genetics , human breast
Background: The study aimed to assess the effect of anti-tumor and anti-proliferative properties of Sambucus nigra (SNA) on MCF-7 and MDA MB-231 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 p53, Bax, Bcl-2, Caspase-3, and 8 levels involved in the apoptotic pathways. ATP binding cassette subfamily B member 4 (ABCB4) gene expression was decreased in MDA‑MB-231 breast cancer cells compared to MCF-7. Also, we observed that DOX, SNA, and DOX + SNA treatment induced expression of Monocarboxylate transporters (MCTs) metabolic pathways such as MCT1 and MCT4. 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-231 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.