Mechanism underlying resveratrol’s attenuation of paclitaxel cytotoxicity in human breast cancer cells: Role of the SIRT1-FOXO1-HER3 signaling pathway

Abstract

ABSTRACT: Resveratrol (RES), a dietary phenolic compound, was reported to have cancer chemoprotective and chemotherapeutic effects. Earlier we unexpectedly observed that RES has a growth-enhancing effect in some breast cancer cells and can diminish the susceptibility of MDA-MB-231 and SKBR-3 cells to paclitaxel-induced cell death, but this phenomenon is not observed in MCF-7 cells. The present study seeks to determine the mechanism underlying RES’s attenuation of paclitaxel cytotoxicity in cancer cells. It is found that RES reduces the anticancer action of paclitaxel only in the human breast cancer cells that express HER3 protein. Treatment of SKBR-3 cells with RES increases HER3 expression in a dose-dependent manner. The induction of HER3 expression by RES confers resistance of breast cancer cells against paclitaxel cytotoxicity. Furthermore, it is observed that the SIRT1-FOXO1 signaling pathway plays an important role in mediating RES-induced upregulation of HER3 expression. In conclusion, the present study reveals the mechanism for RES-induced resistance against paclitaxel in some human breast cancer cells, and it is suggested that the combined use of RES and paclitaxel is not suitable for treating human breast cancer that expresses HER3 protein.

Keywords

• Resveratrol
• Paclitaxel
• SIRT1
• HER3
• FOXO1