Antiprogestin mifepristone inhibits the growth of cancer cells of reproductive and non-reproductive origin regardless of progesterone receptor expression

<p>Abstract</p> <p>Background</p> <p>Mifepristone (MF) has been largely used in reproductive medicine due to its capacity to modulate the progesterone receptor (PR). The study of MF has been expanded to the field of oncology; yet it remains unclear whether the expression of PR is required for MF to act as an anti-cancer agent. Our laboratory has shown that MF is a potent inhibitor of ovarian cancer cell growth. In this study we questioned whether the growth inhibitory properties of MF observed in ovarian cancer cells would translate to other cancers of reproductive and non-reproductive origin and, importantly, whether its efficacy is related to the expression of cognate PR.</p> <p>Methods</p> <p>Dose-response experiments were conducted with cancer cell lines of the nervous system, breast, prostate, ovary, and bone. Cultures were exposed to vehicle or increasing concentrations of MF for 72 h and analysed for cell number and cell cycle traverse, and hypodiploid DNA content characteristic of apoptotic cell death. For all cell lines, expression of steroid hormone receptors upon treatment with vehicle or cytostatic doses of MF for 24 h was studied by Western blot, whereas the activity of the G1/S regulatory protein Cdk2 in both treatment groups was monitored <it>in vitro </it>by the capacity of Cdk2 to phosphorylate histone H1.</p> <p>Results</p> <p>MF growth inhibited all cancer cell lines regardless of tissue of origin and hormone responsiveness, and reduced the activity of Cdk2. Cancer cells in which MF induced G1 growth arrest were less susceptible to lethality in the presence of high concentrations of MF, when compared to cancer cells that did not accumulate in G1. While all cancer cell lines were growth inhibited by MF, only the breast cancer MCF-7 cells expressed cognate PR.</p> <p>Conclusions</p> <p>Antiprogestin MF inhibits the growth of different cancer cell lines with a cytostatic effect at lower concentrations in association with a decline in the activity of the cell cycle regulatory protein Cdk2, and apoptotic lethality at higher doses in association with increased hypodiploid DNA content. Contrary to common opinion, growth inhibition of cancer cells by antiprogestin MF is not dependent upon expression of classical, nuclear PR.</p

Uterotrophic effects of cow milk in immature ovariectomized Sprague–Dawley rats

Milk contains considerable quantities of estrogens and progesterone and as such may be one of the risk factors for hormone-related cancers. To determine the hormonal effects of commercial and traditional types of milk, we performed uterotrophic tests.Forty-five rats were ovariectomized and divided into three groups of 15 animals each. The animals were kept for 7?days on powdered chow and one of three different liquids: commercial milk (C), traditional milk (T), or water. At autopsy, wet and dry uterine weights were determined. The cell heights of the uterine epithelium and endometrium were determined. The uterine 5-bromo-2-deoxyuridine (BrdU) labeling index of the epithelium and endometrium gland epithelium was also assessed.The weights of wet and dry uterus were 142?±?13 and 112?±?10?mg in the C group, 114?±?30 and 91?±?24?mg in the T group, and 87?±?6 and 69?±?5?mg in the W group. Significant differences in wet and dry uterus weights were found between all pairs of groups. The ratio of the wet uterine weight to body weight was significantly higher in the C and T groups than in the W group. The heights of the uterine epithelium and endometrium were higher and BrdU labeling index was greater in the C group than in the T and W groups.Commercially available milk and traditional milk have uterotrophic effects on young ovariectomized rats. Our findings indicate that these uterotrophic effects in the milk groups were partly due to the estrogen and progesterone in the milk.PubMed03162-81