Combination therapy of cisplatin and green silver nanoparticles enhances cytotoxicity and apoptosis in breast cancer cells

Mostafa Heidari Majd1*
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1 Department of Medicinal Chemistry, Faculty of Pharmacy, Zabol University of Medical Sciences, Sistan and Baluchestan, Zabol, Iran
CP 2024, 6(1), 2770
Submitted: 18 January 2024 | Accepted: 15 April 2024 | Published: 15 May 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

Cisplatin is one of the first-line drugs for the treatment of breast cancer and is known for its ability to disrupt cancer cell DNA. However, cisplatin chemotherapy carries side effects and the risk of drug resistance. A strategy to improve its anti-cancer efficacy while reducing its negative effects on health is to leverage the synergistic potential of natural molecules with cisplatin. In this study, we explored combination therapy using cisplatin along with biosynthesized silver nanoparticles (Ag NPs) to enhance apoptosis induction in MCF-7 breast cancer cells while reducing cisplatin resistance. The biosynthesized Ag NPs, derived from Acacia Luciana flower extracts, possess active molecules that effectively inhibit MCF-7 cells. Concurrent administration of cisplatin and Ag NPs resulted in a notable decrease in the IC50 value – approximately 22 – 26 times lower compared to individual treatments of free Ag NPs and cisplatin, respectively. Furthermore, the combination therapy significantly increased the BAK1/BCLX ratio by 162-fold compared to the control, while the cisplatin alone failed to activate intrinsic apoptosis pathway. In addition, the expression level of the CASP3 gene, indicative of the extrinsic pathway of apoptosis, increased approximately 273 times compared to free cisplatin (CASP3 expression = 3.5). Notably, the combination therapy also reduced the expression of the AKT1 gene, associated with cell survival and treatment resistance, when compared to free cisplatin (1.87 vs. 4.488). In conclusion, our findings proved that combination therapy effectively enhances apoptosis induction by cisplatin while reducing drug resistance.

Combination therapy
BAK1/BCLX ratio
Drug resistance
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Conflict of interest
The author declares that he has no competing interests.
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