The Anti‐Proliferative Effect of Resveratrol in T47D Cancer Cell Line is Enhanced by VACM‐1/cul‐5

Abstract

Vasopressin‐activated calcium‐mobilizing (VACM‐1) receptor, a cul‐5 gene product, has been shown to inhibit cellular growth in the T47D breast cancer cell line through a mechanism that involves MAPK phosphorylation and regulation of estrogen receptor (ERα) concentration. As a cul5 gene product, VACM‐1 protein is involved in ubiquitin ligase dependent protein degradation, but factors that regulate its expression and degradation have not been identified. In our search to identify factors/drugs that control VACM‐1 expression, we studied the effects of resveratrol (3,5,4′‐trihydroxy‐trans‐stilbene) which inhibits cellular functions associated with tumor initiation, promotion, and progression by a mechanism that involves inhibition of MAPK phosphorylation, ERα activation and cell cycle arrest. In our study, control and VACM‐1 cDNA transfected T47D breast cancer cells were treated with reservatol and cell growth and VACM‐1 levels were measured. Our data demonstrate that the dose and time dependent effect of resveratol on cellular proliferation is significantly enhanced in cells transfected with VACM‐1 cDNA. Further, our results indicate that expression of VACM‐1 protein is induced by resveratrol. Consequently, these results indicate that the antiproliferative effect of VACM‐1 can be further enhanced by resveratol. This work was supported by a grant from NCI (R15CA104014) and by Dept of Biology.