Study Title:

Curcumin, Hormone Therpapy, and Breast Cancer Risk

Study Abstract

Objective: Combined hormone therapy (HT) containing estrogen and progestin (medroxyprogesterone acetate [MPA]) leads to increased risk of breast cancer in postmenopausal women, compared with HT regimens containing estrogen alone or placebo. We previously reported that in animal models, progestins can accelerate the development of mammary tumors by increasing vascular endothelial growth factor (VEGF) levels. We furthermore showed that curcumin, an Indian spice derived from the turmeric root, specifically inhibits MPA-induced VEGF secretion from breast cancer cells in vitro. In the present study, we investigated whether curcumin inhibits 7,12-dimethylbenz[a]anthracene (DMBA)-induced, MPA-accelerated tumors in Sprague-Dawley rats.

Methods: On day 0, virgin female Sprague-Dawley rats (age, 55 d) were given DMBA (20 mg/rat). Sixty-day timed-release pellets containing 25 mg MPA were implanted into the rats on day 30. Curcumin was administered daily at a rate of 200 mg kg-1 day-1 from days 26 to 50, and animals were killed on day 52 (n = 15-19 per group).

Results: Treatment with curcumin delayed the first appearance of MPA-accelerated tumors by 7 days, decreased tumor incidence by the end of the experiment, and reduced tumor multiplicity in DMBA-induced MPA-accelerated tumors. Curcumin also prevented many of the gross histological changes seen in the MPA-treated mammary gland. Immunohistochemical analyses of mammary tumors showed that curcumin decreased MPA-induced VEGF induction in hyperplastic lesions, although it did not affect the levels of estrogen and progesterone receptors.

Conclusions: We suggest that curcumin be tested as a dietary chemopreventive agent in women already exposed to MPA, in an effort to decrease or delay the risk of breast cancer associated with combined HT.

From press release:

Previous studies have found that postmenopausal women who have taken a combined estrogen and progestin hormone replacement therapy have increased their risk of developing progestin-accelerated breast tumors. Now, University of Missouri researchers have found that curcumin, a popular Indian spice derived from the turmeric root, could reduce the cancer risk for women after exposure to hormone replacement therapy.

"Approximately 6 million women in the United States use hormone replacement therapy to treat the symptoms of menopause," said Salman Hyder, the Zalk Endowed Professorship in Tumor Angiogenesis and professor of biomedical sciences in the College of Veterinary Medicine and the Dalton Cardiovascular Research Center. "This exposure to progestin will predispose a large number of post-menopausal women to future development of breast cancer. The results of our study show that women could potentially take curcumin to protect themselves from developing progestin-accelerated tumors."

In the study, researchers found that curcumin delayed the first appearance, decreased incidence and reduced multiplicity of progestin-accelerated tumors in an animal model. Curcumin also prevented the appearance of gross morphological abnormalities in the mammary glands. In previous studies, MU researchers showed that progestin accelerated the development of certain tumors by increasing production of a molecule called VEGF that helps supply blood to the tumor. By blocking the production of VEGF, researchers could potentially reduce the proliferation of breast cancer cells. Curcumin inhibits progestin-induced VEGF secretion from breast cancer cells, Hyder said.

"Curcumin and other potential anti-angiogenic compounds should be tested further as dietary chemopreventive agents in women already exposed to hormone replacement therapy containing estrogen and progestin in an effort to decrease or delay the risk of breast cancer associated with combined hormone replacement therapy," Hyder said.

The study was coauthored by Hyder; Candace Carroll, graduate student of biomedical sciences; Cynthia Besch-Williford, associate professor of veterinary pathobiology in the MU College of Veterinary Medicine; and Mark Ellersieck, professor and researcher in the MU Experiment Station Statistics.

Study Information

Carroll, Candace E.; Benakanakere, Indira; Besch-Williford, Cynthia; Ellersieck, Mark R.; Hyder, Salman M.
Curcumin delays development of medroxyprogesterone acetate-accelerated 7,12-dimethylbenz[a]anthracene-induced mammary tumors.
Menopause
2009 July
University of Missouri

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