Abstract 578: Apigenin blocks medroxyprogesterone acetate-dependent progression of BT-474 human breast tumor xenografts by inducing apoptosis

Abstract

Abstract Recent clinical and epidemiological evidence suggests that hormone replacement therapy (HRT) containing both estrogen and progestin increases the risk of metastatic breast cancer in post-menopausal women compared with estrogen monotherapy or placebo treated women. The biological mechanisms behind this phenomenon remain obscure. We showed that medroxyprogesterone acetate (MPA), a commonly used progestin in HRT, increases the production of the potent angiogenic growth factor VEGF in breast cancer cells. The anti-progestin RU-486 blocks this effect, suggesting the involvement of progesterone receptors in the process (Int J Cancer, 2001, 92:469). This led to our hypothesis that progestins increase the angiogenic potential of latent tumorigenic cells in the breast, leading to development of palpable tumors. Using a xenograft model that was developed in our laboratory (Cancer Res., 2007, 67:9929), we previously showed that progestins promote the growth and development of BT-474 human xenograft tumors, as well as increasing BT-474 cell metastasis. In this study, we sought to determine whether apigenin, a low molecular weight flavonoid with known anti-carcinogenic properties, inhibits MPA-induced growth of BT-474 xenografts in nude mice. BT-474 human breast cancer cells were inoculated in immune-deficient mice that had been pre-inoculated with estradiol pellets. As was previously reported with this model, estradiol supported a short burst of tumor cell growth, which was followed by tumor regression. Implantation of MPA pellets rescued and stimulated further tumor growth. Administration of apigenin (50 mg/kg i.p.) inhibited the MPA-induced progression and development of BT-474 xenograft tumors. Immunohistochemical analysis revealed that the anti-tumor effects of apigenin occur through induction of tumor cell apoptosis, as measured using TUNEL assay, and also in part by suppression of cell proliferation (Ki67). Apigenin therefore appears to have therapeutic potential against progestin-dependent breast cancer and might be considered as a neutraceutical for treating progestin-dependent tumors in women already exposed to progestins. This study was supported by a COR award from the College of Vet Medicine, and research funds from RADIL, University of Missouri. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 578. doi:1538-7445.AM2012-578