Cell Biology and Toxicology

, Volume 27, Issue 2, pp 95–105 | Cite as

Resveratrol enhances anti-proliferative effect of VACM-1/cul5 in T47D cancer cells

  • Justin Lubbers
  • Steven Lewis
  • Emily Harper
  • Michael P. Hledin
  • Gabriel A. Marquez
  • Alyssa E. Johnson
  • Danelle R. Graves
  • Maria A. Burnatowska-Hledin
Article

Abstract

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.

Keywords

Resveratrol Cell growth VACM-1/cul5 Estrogen receptors 

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Justin Lubbers
    • 1
  • Steven Lewis
    • 1
  • Emily Harper
    • 1
  • Michael P. Hledin
    • 2
  • Gabriel A. Marquez
    • 2
  • Alyssa E. Johnson
    • 1
  • Danelle R. Graves
    • 1
  • Maria A. Burnatowska-Hledin
    • 3
  1. 1.Departments of Biology and Chemistry, Hope CollegeHollandUSA
  2. 2.Holland Public High SchoolHollandUSA
  3. 3.Department of Biology and ChemistryA. Paul Schaap Science Center, Hope CollegeHollandUSA

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