Molecular Effects of The Calcium Channel Blocker Amlodipine on the Sensitivity of Breast Cancer Cells to Doxorubicin

Document Type : Original Article

Authors

1 Molecular Biology Department, Genetic Engineering and Biotechnology Institute, University of Sadat City, Sadat City, Egypt

2 1Molecular Biology Department, Genetic Engineering and Biotechnology Institute, University of Sadat City, Sadat City, Egypt

Abstract

Calcium channel upregulation has been implicated in cancer cell proliferation and progression including in breast cancer. Fortunately, the function of calcium channels can be manipulated pharmacologically using calcium channel blockers (CCBs). Amlodipine, a dihydropyridine CCB, has been demonstrated to exert cytotoxic effects in several types of cancers. The present study evaluated the effects of amlodipine on proliferation, caspase activation, colony formation, and invasion of human breast cancer cells. Methods: We examined the effects of DOX alone or in combination with Amlodipine (AMLO) on the viability of the MCF-7 cells using MTT assay, programmed cell death, and the expression of the anti-apoptotic gene (Bcl‐2) and the pro-apoptotic gene (Bax) by quantitative reverse transcription polymerase chain reaction. Combination index (CI) values were calculated using CompuSyn. Results: we found that adding AMLO to DOX potentiated its antiproliferation effect. The value of the combination index (CI) of DOX/AMLO was less than 1 indicating a synergistic effect. Combined DOX/AMLO treatment also caused potentiated apoptosis more than DOX‐single treatment. At the molecular levels, DOX/AMLO treatment downregulated the mRNA of Bcl‐2; while upregulated the Bax gene compared with DOX alone. Conclusion: the results confirmed the potential of AMLO in sensitizing Breast cancer to DOX by targeting suppressing the Bcl-2 gene while upregulating the Bax gene. Additionally, AMLO could be repurposed to reduce the therapeutic doses of DOX as indicated by the dose reduction index (DRI) and subsequently decrease its side effects (especially cardiotoxicity), along with chemosensitization of breast cancer cells to DOX treatment.

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Egyptian Journal of Chemistry
Volume 65, Issue 132 - Serial Number 13
Special Issue: Chemistry and Global Challenges (Part B)
December 2022
Pages 1001-1007

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History

  • Receive Date: 11 August 2022
  • Revise Date: 19 August 2022
  • Accept Date: 31 August 2022

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