Curcumin delays development of medroxyprogesterone acetate-accelerated 7,12-dimethylbenz[a]anthracene-induced mammary tumors.
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.
Carroll
Candace E
CE
Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA.
Benakanakere
Indira
I
Besch-Williford
Cynthia
C
Ellersieck
Mark R
MR
Hyder
Salman M
SM
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D019587:Dietary Supplements; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017258:Medroxyprogesterone Acetate; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D015127:9,10-Dimethyl-1,2-benzanthracene; D017258:Medroxyprogesterone Acetate; D003474:Curcumin