*Article* **Nanoformulation of Polyphenol Curcumin Enhances Cisplatin-Induced Apoptosis in Drug-Resistant MDA-MB-231 Breast Cancer Cells**

**Parastoo Karami 1, Goran Othman 2,3, Zjwan Housein 2, Abbas Salihi 4,5, Mohammad Ali Hosseinpour Feizi 1, Hewa Jalal Azeez <sup>1</sup> and Esmaeil Babaei 1,\***


**Abstract:** Triple Negative Breast Cancer (TNBC) is the aggressive and lethal type of breast malignancy that develops resistance to current therapies. Combination therapy has proven to be an effective strategy on TNBC. We aimed to study whether the nano-formulation of polyphenolic curcumin (Gemini-Cur) would affect the cisplatin-induced toxicity in MDA-MB-231 breast cancer cells. MDA-MB-231 cells were treated with Gemini-Cur, cisplatin and combination of Gemini-Cur/Cisplatin in a time- and dose-dependent manner. Cell viability was studied by using MTT, fluorescence microscopy and cell cycle assays. The mode of death was also determined by Hoechst staining and annexin V-FITC. Real-time PCR and western blotting were employed to detect the expression of BAX and BCL-2 genes. Our data demonstrated that Gemini-Cur significantly sensitizes cancer cells to cisplatin (combination index ≤ 1) and decreases IC50 values in comparison with Gemini-cur or cisplatin. Further studies confirmed that Gemini-Cur/Cisplatin suppresses cancer cell growth through induction of apoptosis (*p* < 0.001). In conclusion, the data confirm the synergistic effect of polyphenolic curcumin on cisplatin toxicity and provide attractive strategy to attain its apoptotic effect on TNBC.

**Keywords:** polyphenolic curcumin; cisplatin; combination therapy; breast cancer; apoptosis; gemini surfactant nanoparticles
