Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of immature 21-day-old female Sprague-Dawley rats with 17 beta-estradiol (E2) (0.5 microgram/rat) caused a significant increase in uterine wet weight, DNA synthesis, progesterone receptor (PR) binding, and peroxidase activity. At doses as high as 40 mg/rat, the bioflavonoid naringenin did not cause a significant increase in any of these E2-induced responses. However, in rats cotreated with E2 (0.5 microgram/rat) plus naringenin (30 mg/rat); there was a significant decrease in E2-induced uterine wet weight, DNA synthesis, PR binding, and peroxidase activity, indicating that naringenin exhibits antiestrogenic activity in the immature rodent uterus. The binding of uterine nuclear extracts to a 32P-labeled estrogen responsive element (ERE) or progesterone responsive element (PRE) was determined using gel electrophoretic band shift assays. Incubation of [32P]ERE with uterine nuclear extracts from rats treated with naringenin or E2 resulted in the formation of estrogen receptor (ER):ERE complexes; a higher mobility complex was prominent in the extracts from E2-treated rats, whereas a lower mobility complex was observed using nuclear extracts from naringenin-treated animals. There was a significant decrease in the intensity of the E2-induced complex using nuclear extracts from rats treated with E2 plus naringenin. In contrast, transformed cytosol from control rats gave an intense ER:ERE complex, whereas the intensity of the band was decreased markedly using transformed uterine cytosol from treated rats. Formation of a PR:PRE complex was also determined using transformed uterine cytosol. Cytosol from E2-treated rats gave an intense retarded band, whereas only weak bands were observed using cytosols from DMSO- (solvent), naringenin-, or naringenin plus E2-treated cells. The results of in vitro studies showed that 1 nM E2 increased (3- to 4-fold) the growth of MCF-7 human breast cancer cells, whereas 1-1000 nM naringenin had no effect on cell proliferation. In cells cotreated with 1 nM E2 plus 1000 nM naringenin, there was a significant decrease in E2-induced cell growth. In MCF-7 cells transiently transfected with a pS2 promoter-regulated luciferase reporter gene, naringenin exhibited weak estrogenic activity. In cells cotreated with 0.1 or 1.0 microM naringenin plus 1 nM E2, naringenin inhibited E2-induced luciferase activity. The results of these studies confirmed that naringenin is a weak estrogen that also exhibits partial antiestrogenic activity in the female rat uterus and MCF-7 human breast cancer cells.
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PMID:Naringenin: a weakly estrogenic bioflavonoid that exhibits antiestrogenic activity. 750

Despite the wide use of Chinese licorice root (Glycyrrhiza uralensis) for the treatment of menopausal complaints, little is known on its potential estrogenic properties, and available information relative to its effects on cell proliferation is contradictory. In this study, the estrogenic properties of licorice root were evaluated in vitro by use of several assays. The effects of increasing concentrations of a DMSO extract of licorice root on the growth of MCF-7 breast cancer cells were biphasic. The extract showed an ER-dependent growth-promoting effect at low concentrations and an ER-independent anti-proliferative activity at high concentrations. In further experiments, licorice root was sequentially extracted to yield four fractions: hexane, EtOAc, methanol and H(2)O. Only the EtOAc extract had effects on cell proliferation similar to the DMSO extract. The hexane extract had no effect on cell growth. In contrast, the methanol and water extracts showed an ER-independent, growth-promoting effect. Similar to its effects on cell proliferation, the EtOAc extract had a biphasic effect on S phase cell cycle distribution and the level of PCNA protein. This extract-induced transactivation of endogenous ERalpha in MCF-7 cells, supported by inducing down-regulation of ERalpha protein and mRNA levels, and up-regulation of ERalpha target genes pS2 and GREB1. These results suggest that the activity of licorice root and the balance between increased risk for cancer and prevention of estrogen-dependent breast cancer may depend on the amount of dietary intake.
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PMID:Estrogenic activities of extracts of Chinese licorice (Glycyrrhiza uralensis) root in MCF-7 breast cancer cells. 1916 97