Epidemiological and laboratory studies support the use of the plant-derived flavonoid apigenin as a potential nutraceutical for preventing a number of different cancers. However the effect of dietary apigenin on prevention of progestin-accelerated breast tumors has hitherto not been explored. Medroxyprogesterone acetate (MPA) is the most commonly used synthetic progestin administered to post-menopausal women for hormone replacement therapy. MPA accelerates the development of breast cancers by reducing tumor latency and increasing tumor incidence and multiplicity in a DMBA-induced breast cancer model, and causes progression of human cancer cells in xenografts (Clin Can Res, 2006, 12:4062; Cancer Res, 2007, 67: 9929). Previously we showed that intraperitoneally administered apigenin effectively treated and prevented the progression of MPA-accelerated breast cancer in both the DMBA-induced, and xenograft mammary cancer models (Cancer Prev Res, 2011, 4: 1316; Horm Canc, 2012, 3: 160). In the present study we used the DMBA model to examine the chemopreventive effect of dietary apigenin against MPA-accelerated tumors. Based on reports in the literature, we examined the effects of feeding 3 different dietary levels of apigenin (0.02%, 0.1% and 0.5% wt/wt) in a phytoestrogen-free diet following treatment with DMBA, and prior to implantation of MPA pellets which accelerate tumor development. The MPA-dependent tumor incidence was lower in the 0.1% dietary apigenin treatment group. Surprisingly, the same dietary level significantly increased tumor multiplicity in those animals that developed tumors. A five-fold increase (0.5%) or reduction (0.02%) in dietary apigenin failed to reduce MPA-dependent tumor incidence and the higher dose (0.5%) substantially increased tumor multiplicity compared with MPA alone. Tumor incidence and multiplicity were unaffected in apigenin-fed animals that were treated with DMBA but supplemented with placebo pellets. There were no morphological or histological differences between tumors from animals fed apigenin-supplemented diets and those given a control diet, either in the presence or absence of MPA.These findings show that apigenin, given in a diet devoid of phytochemicals, exacerbated the effects of MPA on tumor development and multiplicity in a chemically-induced breast cancer model. Consequently, until further research clarifies the effect of dietary apigenin on progestin-accelerated tumors, caution should be exercised when considering the flavonoid as a dietary supplement for preventing hormone-dependent breast cancer. Supported by a COR award from University of Missouri, and research funds from RADIL.

Citation Format: Benford Mafuvadze, Matthew Cook, Xu Zhang, Cindy Besch-Williford, Salman M. Hyder. Complex effects of dietary apigenin on prevention of MPA-accelerated DMBA-induced mammary tumors in Sprague-Dawley rats. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3694. doi:10.1158/1538-7445.AM2013-3694