Abstract 4159: Therapeutic effects of luteolin against progestin-dependent breast cancer involves induction of apoptosis, and suppression of both stem-cell-like cells and angiogenesis

Clinical and epidemiological evidence show that combined estrogen (E) and progestin (P) hormone replacement therapy (HRT) increases the risk of breast cancer in postmenopausal women. Tumor progression is dependent on cell survival and angiogenesis, which provides nutrients vital to the developing cancer. We have shown that physiological levels of P (10 nM), including medroxyprogesterone acetate (MPA), which is widely used in HRT, increases the production of the potently angiogenic vascular endothelial growth factor (VEGF), in human breast cancer cells both in vitro and in vivo. The anti-progestin RU-486 blocks this effect, suggesting the involvement of progesterone receptors in the process (Int J Cancer, 2001, 92:469). Evidence from our laboratory using in vivo breast cancer models suggests that P accelerates the development of tumors from latent tumorigenic cells, leading to the development of palpable tumors (Cancer Res., 2007, 67:9929; Clin Can Res, 2006, 12:4062), a process that may be attributed to increased production of VEGF. RU-486 blocks P-dependent VEGF production and thereby reduces tumor growth; however, the anti-progestin has severe side-effects and therefore cannot be used in the long-term. Recently, we have been studying less toxic naturally-occurring compounds for their ability to block P-dependent tumor progression. We tested the effects of the flavonoid luteolin, which is commonly found in fruits and vegetables, on proliferation of BT-474 and T47-D breast ca...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Tumor Biology Source Type: research