Resveratrol inhibits proliferation and induces apoptosis via the Hippo/YAP pathway in human colon cancer cells.

ABSTRACT

High malignancy and mortality in colon cancer require clarifying the underlying mechanisms of colon cancer carcinogenesis and exploring new targets or drugs for the clinical treatment of colon cancer. Resveratrol (Res), a natural compound, shows cytotoxicity against various tumors. However, the specific anti-cancer mechanism of Res remains unclear. In the present study, we aimed to explore the anti-cancer activity of Res against colon cancer cells and the possible mechanism. The results showed that Res could inhibit cell proliferation and induce cell cycle arrest and apoptosis in HCT116 cells. Western blotting and Polymerase chain reaction (PCR) showed that Res increased the phosphorylated YAP (pYAP) levels and decreased YAP total protein level and decreased the mRNA expression of the YAP signaling downstream genes CTGF and CYR61. The effects of Res on pYAP were enhanced by YAP inhibitor verteporfin (VP). VP also enhanced the effects of Res on decreasing viability and inducing apoptosis. Furthermore, the molecular docking analysis indicated Res could bind with YAP-TEAD through van der Waals, pi-alkyl, and pi-pi stacked interactions. Our findings suggested that the anti-cancer activity of Res may be mediated via activating Hippo/YAP signaling and partially disturbing the interaction between YAP and TEAD. All this evidence supports that Res may be an efficacious drug for colon cancer treatment.