Molecular Effects of The Calcium Channel Blocker Amlodipine on the Sensitivity of Breast Cancer Cells to Doxorubicin | ||||
| Egyptian Journal of Chemistry | ||||
| Volume 65, Issue 132, December 2022, Page 1001-1007 PDF (631.95 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/ejchem.2022.155712.6730 | ||||
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| Authors | ||||
| Reham M. Abdel Moneim1; Hanan M El Henfay1; Mahmoud Lotfy2; Mohammed F. Elshal* 1 | ||||
| 1Molecular Biology Department, Genetic Engineering and Biotechnology Institute, University of Sadat City, Sadat City, Egypt | ||||
| 21Molecular 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. | ||||
| Keywords | ||||
| Apoptosis; calcium channel blocker; chemoresistance; doxorubicin; Amlodipine | ||||
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