Resveratrol enhances anti-proliferative effect of VACM-1/cul5 in T47D cancer cells
Vasopressin-activated calcium-mobilizing (VACM-1) protein is a cul-5 gene product that forms complexes with a subclass of ubiquitin E3 ligases involved in proteasomal protein degradation. The expression of VACM-1 cDNA in the T47D breast cancer cell line inhibits growth and decreases phosphorylation of mitogen activated protein kinase. Factors that regulate expression or stability of VACM-1 protein have not been identified, however. In our search to identify drugs/substances that may control VACM-1 protein expression, we examined the effects of resveratrol (trans-3,5,4′-trihydroxystilbene), a natural component in the human diet which inhibits tumor initiation and promotion. CMV vector and VACM-1 cDNA stably transfected T47D breast cancer-derived cells were treated with resveratrol and cell growth and VACM-1 protein concentrations were measured. Since the cellular mechanism of resveratrol-dependent inhibition of cell growth also involves the regulation of estrogen receptors, the effect of 17-β−estradiol and resveratrol on ERα levels and on cell growth was examined in control and in VACM-1 cDNA transfected cells. Our results demonstrate that antiproliferative effect of resveratrol observed in the control T47D cancer cells was significantly enhanced in VACM-1 cDNA transfected T47D cells. Western blot results indicated that resveratrol increased VACM-1 protein concentration. Finally, treatment with resveratrol for 24 and 48 h attenuated 17-β−estradiol induced increase in cell growth both in control and in VACM-1 cDNA transfected cells. The effect was significantly higher in the VACM-1 cDNA transfected cells when compared to controls. These results indicate that the antiproliferative effect of resveratrol may involve induction of VACM-1/cul5.
KeywordsResveratrol Cell growth VACM-1/cul5 Estrogen receptors
- Brownson DM, Azios NG, Fuqua BK, Dharmawardhane SF, Mabry TJ. Am Soc Nutr Sci. 2002;2:3482S–9S.Google Scholar
- Burnatowska-Hledin M, Spielman WS, Smith WL, Shi P, Meyer JM, Dewitt DL. Am J Physiol. 1995;268:1198–210.Google Scholar
- Chan AYM, Dolinsky VW, Soltys CLM, Baksh S, Light PE, Dyck JRB. J Biol Chem. 2008;283:24914–201.Google Scholar
- Petroski MD, Deshaies RJ. Nature. 2005;6:9–22.Google Scholar
- Van Dort CV, Zhao P, Parmelee K, Capps B, Poel A, Listenberger L, et al. Am J Physiol Cell Physiol. 2003;285:1386–96.Google Scholar