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.
Lubbers
Justin
J
Department of Biology, Hope College, Holland, MI 49422-9000, USA.
Lewis
Steven
S
Harper
Emily
E
Hledin
Michael P
MP
Marquez
Gabriel A
GA
Johnson
Alyssa E
AE
Graves
Danelle R
DR
Burnatowska-Hledin
Maria A
MA
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D044842:Cullin Proteins / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D006801:Humans; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014162:Transfection
C496871:CUL5 protein, human; D044842:Cullin Proteins; D018076:DNA, Complementary; D047628:Estrogen Receptor alpha; D013267:Stilbenes; D004958:Estradiol; D000077185:Resveratrol