Curcumin inhibits MPA-induced secretion of VEGF from T47-D human breast cancer cells.
OBJECTIVE
Recent clinical trials show that women who receive combined estrogen and progestin hormone therapy (HT) have a higher risk of breast cancer than women who receive estrogen alone or placebo. We have shown that progestins stimulate expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, in human breast cancer cells that express the progesterone receptors and mutant p53 protein. Because increased levels of VEGF promote tumor progression, compounds that prevent progestin-induced expression of VEGF could be clinically useful. The objective of this study was to examine whether the polyphenol compound curcumin has the capacity to block progestin-induced secretion of VEGF from T47-D human breast cancer cells.


METHODS
The estrogen and progesterone receptor containing T47-D human breast cancer cells was exposed to 10 nM progesterone or synthetic progestins and varying concentrations of curcumin to determine whether curcumin blocks progestin-dependent production of VEGF from tumor cells.


RESULTS
Curcumin (0.001-10 microM for 18 h) reduced medroxyprogesterone acetate (MPA)-induced secretion of VEGF from T47-D cells in a dose-dependent manner. Secretion of VEGF from cells treated with progesterone or progestins other than MPA was unaffected by curcumin.


CONCLUSIONS
MPA is the most widely used progestin in HT. Curcumin may therefore provide a clinically useful tool for the suppression of MPA-induced elaboration of VEGF by tumor cells. We propose therefore that clinical trials to assess the beneficial effects of curcumin in postmenopausal women are warranted.
Carroll
Candace E
CE
Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA.
Ellersieck
Mark R
MR
Hyder
Salman M
SM
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000517:prevention & control*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000037:antagonists & inhibitors; D009376:Neoplasms, Hormone-Dependent / Q000517:prevention & control*; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D017258:Medroxyprogesterone Acetate; D003474:Curcumin