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)

  • سال انتشار: 1401
  • محل انتشار: فصلنامه سرطان پستان، دوره: 9، شماره: 1
  • کد COI اختصاصی: JR_ARCHB-9-1_010
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 138
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نویسندگان

Ali Ghanbari

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

Shiva Roshankhah

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

Mohammad Reza Salahshoor

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

Cyrus Jalili

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

چکیده

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

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