Targeting 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)

Archives of Breast Cancer

article

AliGhanbari¹  ShivaRoshankhah¹  Mohammad RezaSalahshoor¹  CyrusJalili¹  Mojtaba Esmaeli¹ 

[1] Medical Biology Research Center, Kermanshah University of Medical Sciences

关键词: Breast cancer;    Doxorubicin;    Drug resistance;    Sambucus nigra;   

DOI  :  10.32768/abc.20229183-95

学科分类：社会科学、人文和艺术（综合）

来源: Kaviani Breast Disease Institute

【 摘 要 】

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.

【 授权许可】

CC BY-NC