The Antitumor Effect of Capsaicin on Prostate Cancer Cells Depends on AMPK Activation Through LKB1 Kinase and TRPV1 Receptor

Abstract

Recently, natural compounds and their derivatives have been reported to have anti-cancer effects. Herein, we investigated the mechanism whereby the natural vanilloid capsaicin exerts anti-tumor effects on prostate cancer cells. We found that capsaicin activates the AMP-activated kinase (AMPK) and promotes cell death in the LKB1 expressing prostate cancer cell lines LNCaP and PC3 but not in the LKB1-null cell line DU-145. Capsaicin treatment stimulated LKB1 phosphorylation and activated AMPK in LKB1 expressing cells. In addition, overexpression of LKB1 by lentiviral infection in DU-145 cells, induced capsaicin-triggered AMPK activation and apoptosis while LKB1 silencing in LNCaP and PC3 cells, increased capsaicin-promoted cell death. Capsaicin-induced LKB1 phosphorylation, was dependent on the transient receptor potential cation channel subfamily V member 1 (TRPV1), since TRPV1 knocked down by shRNA, abolished LKB1 and AMPK phosphorylation and inhibited apoptosis. Altogether, our results show that capsaicin affect AMPK activity in an LKB1- and TRPV1-dependent fashion, linking TRPV1 with cell fate. These data also suggest that capsaicin may be a rational therapeutic option for prostate tumors.