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- W2334258518 abstract "Post-menopausal women undergoing hormone replacement therapy (HRT) containing both progestins (P) and estrogens (E) are at an increased risk of developing breast cancer compared with those taking E alone. The biological mechanisms behind this phenomenon however, remain obscure. We showed that medroxyprogesterone acetate (MPA), a commonly used P, increases the production of the potent angiogenic growth factor VEGF in breast cancer cells that was blocked by the anti-progestin RU-486 suggesting the involvement of progesterone receptors (Int J Cancer, 2001, 92:469). This led to our hypothesis that P increases the angiogenic potential of latent tumorigenic cells in the breast, leading to development of palpable tumors. To prove this hypothesis, we developed in vivo models with human xenografts in mice (Cancer Res., 2007, 67:9929), and DMBA-induced tumors in rats (Clin Can Res, 2006, 12:4062). In both models, MPA accelerated tumor development that was blocked by RU-486. Since RU-486 has severe side-effects, we undertook studies aimed at identifying less toxic naturally-occurring compounds that might prevent P-dependent VEGF induction and tumor acceleration. We recently identified apigenin, a low molecular weight flavonoid commonly found in fruits and vegetables, which inhibited MPA-induced VEGF secretion from human breast cancer cells (Menopause, 2010, 17:1055). In this study we used the DMBA-induced mammary tumor model to determine whether apigenin prevents the development of P-accelerated tumors in vivo. Female Sprague-Dawley rats were treated with DMBA by oral gavage (Day 1). Seven days prior to implantation of 25 mg/60 day release MPA pellets (Day 28), ip administration of apigenin (50 mg/kg daily) began, and continued for 10 days. Animals were palpated for tumors every second day and experiment was terminated 60 days after DMBA treatment was initiated. Apigenin treatment led to a significant delay in the appearance of the first tumor, compared with MPA alone (56 vs 41 days; p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1844. doi:10.1158/1538-7445.AM2011-1844" @default.
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- W2334258518 date "2011-04-15" @default.
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- W2334258518 title "Abstract 1844: Apigenin prevents development of progestin-accelerated 7,12-dimethylbenz(a) anthracene (DMBA)-induced mammary tumors in Sprague-Dawley rats" @default.
- W2334258518 doi "https://doi.org/10.1158/1538-7445.am2011-1844" @default.
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