Synergistic Apoptotic Effects of Cisplatin and Arbutin in MCF-7 Breast Cancer Cells

Abstract

Objective: Cisplatin is a key component in cancer treatment, but its effectiveness can be limited by dose related toxicities. Combining it with natural compounds such as arbutin offers a promising approach to improve treatment outcomes while reducing side effects. This study aimed to explore the combined apoptotic effects of arbutin and cisplatin in MCF-7 breast cancer cells, specifically focusing on mitochondrial gene expression. Methods: MCF-7 cells were treated for 48 hours with arbutin, cisplatin, or a combination of both at fixed ratios. Cytotoxicity and synergy were evaluated using the Chou-Talalay median-effect method. Nuclear morphology, indicative of apoptosis, was assessed through Hoechst 33342 staining. Gene expression analysis targeted mitochondrial dynamics (DRP1, Fis1, MFN1, MFN2), oxidative stress markers (SOD2, GPx), apoptosis indicators (Bcl2), autophagy (Beclin1), and prostaglandin pathways (PGF2α, PGF2β), with results normalized to β-actin. Results: The combination therapy significantly enhanced cytotoxicity compared to individual treatments (Combination Index <1). Hoechst staining revealed increased nuclear condensation and fragmentation, clear indicators of apoptosis. Among the genes analyzed, only PGF2β showed a significant downregulation in cells treated with the combination (p<0.05). Trends indicated elevated levels of DRP1 and Fis1, while MFN1 and MFN2 levels were decreased, suggesting a shift towards mitochondrial fragmentation, despite the results not reaching statistical significance. Conclusion: The combination of arbutin and cisplatin promotes apoptosis in MCF-7 cells, potentially due to changes in mitochondrial dynamics. These findings indicate that arbutin may enhance the efficacy of cisplatin, potentially allowing for reduced cisplatin doses and a lower risk of side effects.

Keywords

• Cisplatin
• Arbutin
• MCF-7
• Apoptosis
• Mitochondria

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