title: Effects of dietary apigenin on tumor latency, incidence and multiplicity in a medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced breast cancer model.
abstract: Medroxyprogesterone acetate (MPA) is a synthetic progestin commonly administered to postmenopausal women for hormone replacement therapy and has been associated with increased risk of breast cancer. MPA has been shown to accelerate the development of mammary tumors in a 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer animal model. Previously, we have shown that intraperitoneally administered apigenin effectively treated and prevented the progression of MPA-accelerated breast cancer in DMBA-induced and xenograft mammary cancer models. Here we used the DMBA model to examine the chemopreventive effect of dietary apigenin against MPA-accelerated tumors with 3 different levels of apigenin (0.02%, 0.1%, and 0.5% w/w) incorporated into a phytoestrogen-free diet. Results showed that 0.1% dietary apigenin reduced MPA-dependent tumor incidence; however, the same dietary level increased tumor multiplicity in animals that developed tumors. Neither 0.02% nor 0.5% dietary apigenin reduced MPA-dependent tumor incidence or latency, and tumor multiplicity increased significantly in response to 0.5% apigenin. These results contrast with previous chemopreventive effects observed when apigenin was administered intraperitoneally, suggesting that route of administration may influence its action. Consequently, until further research clarifies the effect of dietary apigenin on progestin-accelerated mammary tumors, caution should be exercised when considering the flavonoid as a dietary supplement for preventing hormone-dependent breast cancer.
authors.affiliation: a Department of Biomedical Sciences and Dalton Cardiovascular Research Center , University of Missouri , Columbia , Missouri , USA.
authors.forename: Benford
authors.initials: B
authors.lastname: Mafuvadze
authors.forename: Matthew
authors.initials: M
authors.lastname: Cook
authors.forename: Zhang
authors.initials: Z
authors.lastname: Xu
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Besch-Williford
authors.forename: Salman M
authors.initials: SM
authors.lastname: Hyder
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D047310:Apigenin / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000009:adverse effects*; D017698:Postmenopause / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015127:9,10-Dimethyl-1,2-benzanthracene; D047310:Apigenin; D017258:Medroxyprogesterone Acetate