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)

Ali  Ghanbari; Shiva  Roshankhah; Mohammad Reza  Salahshoor; Cyrus  Jalili; Mojtaba Esmaeli

doi:10.32768/abc.20229183-95

Ali Ghanbari ⁽¹⁾, Shiva Roshankhah ⁽²⁾, Mohammad Reza Salahshoor ⁽³⁾, Cyrus Jalili ⁽⁴⁾, Mojtaba Esmaeli ⁽⁵⁾

(1) Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran, Iran, Islamic Republic of,

(2) Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran, Iran, Islamic Republic of,

(3) Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran, Iran, Islamic Republic of,

(4) Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran, Iran, Islamic Republic of,

(5) Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran, Iran, Islamic Republic of

https://doi.org/10.32768/abc.20229183-95

Issue
Volume 9, Issue 1, February 2022

Submitted
September 22, 2021

Published
January 23, 2022

Keywords:

Breast cancer, Doxorubicin, Drug resistance, Sambucus nigra

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Abstract

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.

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