Curcumin-Etoposide Synergy: Unveiling the Molecular Mechanisms of Enhanced Apoptosis and Chemoresistance Attenuation in Breast Cancer

姜黄素-依托泊苷协同作用:揭示乳腺癌细胞凋亡增强和化学抗性减弱的分子机制

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作者:Bahar Jaberian Asl, Reza Afarin, Mahdi Hatami, Amineh Dehghani Madiseh, Mohammadreza Roshanazadeh, Mojtaba Rashidi

Background

Combining natural compounds with chemotherapeutic agents has emerged as a promising approach for cancer treatment. Curcumin (Cur), a natural polyphenol, is known for its anti-cancer properties, including the ability to induce apoptosis and arrest cell cycle progression. Objectives: This study aimed to evaluate the effects of Cur and etoposide (ETO), both individually and in combination, on the induction of apoptosis in breast cancer (BC) cell lines.

Conclusions

Cur has the potential to amplify ETO-induced apoptosis in BC cells. This combination may offer a promising therapeutic approach for BC.

Methods

The impact of Cur and ETO on cell proliferation was assessed using MTT viability assays. Apoptosis induction by these drugs was evaluated through Annexin V flow cytometry and caspase-3 and caspase-9 activity assays. Quantitative real-time PCR was employed to measure Bax and Bcl-2 gene expression levels. Western blotting was conducted to determine protein levels of p53, p21, Bax, and Bcl-2.

Results

A non-significant dose of ETO was selected based on MTT assay results and combined with 75 µM of Cur. Curcumin enhanced ETO's pro-apoptotic effect by increasing caspase activities. The combination of Cur and ETO significantly reduced Bcl-2 gene expression while upregulating Bax expression. Furthermore, treatment with this combination elevated the protein levels of p53, p21, and Bax, compared to ETO or Cur alone, while significantly decreasing Bcl-2 protein levels. Conclusions: Cur has the potential to amplify ETO-induced apoptosis in BC cells. This combination may offer a promising therapeutic approach for BC.

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