The reversal effect of capsaicin on doxorubicin-resistant breast cancer cells

doi:10.5246/jcps.2021.08.054

Abstract

Abstract:

Overexpression of P-glycoprotein (P-gp), encoded by the MDR1 gene, in tumor cells curtails the efficacy of chemotherapy, leading to multidrug resistance (MDR), which can be reversed by the P-gp inhibitor. Capsaicin, the principal pungent component of hot chili, is a reported P-gp inhibitor with anti-cancer properties. In the present study, we aimed to evaluate the MDR reversal effect of capsaicin. The MCF-7/DOX cells were treated with capsaicin for a short term (3 h) or long term (72 h). The cytotoxicity studies were completed by using the SRB method. RT-PCR method was utilized to evaluate the effect of capsaicin on the expression of MDR1 at the mRNA level. The accumulation and subcellular distribution studies were implemented to further investigate the reversal effect of capsaicin. The effect of capsaicin on the ATP production of mitochondria was also evaluated. The results of the cytotoxicity study indicated that capsaicin (50 μM) reversed the resistance of MCF-7/DOX cells to doxorubicin (DOX) with the reversal fold of 4.68, and concentration-dependently down-regulated the expression of MDR1 at the mRNA level after long-term (72 h) incubation. After short-term (3 h) incubation, capsaicin reversibly and concentration-dependently increased the accumulation of DOX into MCF-7/DOX cells and induced a different subcellular distribution of DOX compared with verapamil as a positive control. The ATP production of mitochondria was also concentration-dependently inhibited by capsaicin. In conclusion, capsaicin was capable of reversing the resistance of MCF-7/DOX cells to DOX, making it a promising lead compound for MDR reversal.

Key words: MDR1, Capsaicin, MCF-7/DOX, P-glycoprotein

Supporting:

Yi Zhou, Ting Wang, Jiajia Zhao, Xuehua Jiang. The reversal effect of capsaicin on doxorubicin-resistant breast cancer cells[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(8): 666-674.

Figures/Tables 8

Table 1. Cytotoxicity of DOX with or without capsaicin in MCF-7/DOX cells.

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