Apigenin prevents development of medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumors in Sprague-Dawley rats.

The use of progestins as a component of hormone replacement therapy has been linked to an increase in breast cancer risk in postmenopausal women. We have previously shown that medroxyprogesterone acetate (MPA), a commonly administered synthetic progestin, increases production of the potent angiogenic factor vascular endothelial growth factor (VEGF) by tumor cells, leading to the development of new blood vessels and tumor growth. We sought to identify nontoxic chemicals that would inhibit progestin-induced tumorigenesis. We used a recently developed progestin-dependent mammary cancer model in which tumors are induced in Sprague-Dawley rats by 7,12-dimethylbenz(a)anthracene (DMBA) treatment. The flavonoid apigenin, which we previously found to inhibit progestin-dependent VEGF synthesis in human breast cancer cells in vitro, significantly delayed the development of, and decreased the incidence and multiplicity of, MPA-accelerated DMBA-induced mammary tumors in this animal model. Whereas apigenin decreased the occurrence of such tumors, it did not block MPA-induced intraductal and lobular epithelial cell hyperplasia in the mammary tissue. Apigenin blocked MPA-dependent increases in VEGF, and suppressed VEGF receptor-2 (VEGFR-2) but not VEGFR-1 in regions of hyperplasia. No differences were observed in estrogen or progesterone receptor (ER/PR) levels, or the number of estrogen receptor-positive cells, within the mammary gland of MPA-treated animals administered apigenin, MPA-treated animals, and placebo treated animals. However, the number of progesterone receptor-positive cells was reduced in animals treated with MPA or MPA and apigenin compared with those treated with placebo. These findings suggest that apigenin has important chemopreventive properties for those breast cancers that develop in response to progestins.
AuthorsBenford Mafuvadze, Indira Benakanakere, Franklin R López Pérez, Cynthia Besch-Williford, Mark R Ellersieck, Salman M Hyder
JournalCancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 4 Issue 8 Pg. 1316-24 (Aug 2011) ISSN: 1940-6215 [Electronic] United States
PMID21505181 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Placebos
  • Receptors, Progesterone
  • Vascular Endothelial Growth Factor A
  • 9,10-Dimethyl-1,2-benzanthracene
  • Apigenin
  • Medroxyprogesterone Acetate
  • Vascular Endothelial Growth Factor Receptor-2
  • 9,10-Dimethyl-1,2-benzanthracene (pharmacology)
  • Animals
  • Apigenin (metabolism, pharmacology)
  • Dose-Response Relationship, Drug
  • Female
  • Immunohistochemistry (methods)
  • Mammary Neoplasms, Animal (drug therapy)
  • Medroxyprogesterone Acetate (metabolism)
  • Neovascularization, Pathologic
  • Placebos
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Progesterone (metabolism)
  • Vascular Endothelial Growth Factor A (metabolism)
  • Vascular Endothelial Growth Factor Receptor-2 (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: