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

In our study, we present experimental evidence suggesting that curcumin exerts multiple different suppressive effects on human breast carcinoma cells in vitro. Our experiments demonstrate that curcumin's antiproliferative effects are estrogen dependent in ER (estrogen receptor)-positive MCF-7 cells, being more pronounced in estrogen-containing media and in the presence of exogenous 17-beta estradiol. Curcumin inhibits the expression of ER downstream genes including pS2 and TGF-beta (transforming growth factor) in ER-positive MCF-7 cells, and this inhibition is also dependent on the presence of estrogen. Curcumin also decreases ERE (estrogen responsive element)-CAT activities induced by 17-beta estradiol. In addition, we demonstrate that curcumin exerts strong anti-invasive effects in vitro that are not estrogen dependent in the ER-negative MDA-MB-231 breast cancer cells. These anti-invasive effects appear to be mediated through the downregulation of MMP-2 (matrix metalloproteinase) and the upregulation of TIMP-1 (tissue inhibitor of metalloproteinase), 2 common effector molecules that have been implicated in regulating tumor cell invasion. Our study also demonstrates that curcumin inhibits the transcript levels of 2 major angiogenesis factors VEGF (vascular endothelial growth factor) and b-FGF (basic fibroblast growth factor) mainly in ER-negative MDA-MB-231 cells.
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PMID:Curcumin exerts multiple suppressive effects on human breast carcinoma cells. 1185 14

Plant-derived estrogen-like compounds, or phytoestrogens, are given much attention due to their potential therapeutic use. In this study, xanthorrhizol, a natural sesquiterpenoid isolated from the rhizome of Curcuma xanthorrhiza ROXB. (Zingiberaceae), was evaluated for its estrogenic activity. It has been known that compounds acting as ligands for estrogen receptors (ERs) are considered to possess estrogenic activity. Therefore, the Gal-4/ER transactivation assay in transiently transfected African green monkey kidney (COS-7) cells was used to examine the estrogenic activity of xanthorrhizol. Both subtypes of ERs, ERalpha and ERbeta, were involved in this assay. Further transactivation assays and pS2 mRNA analysis were also conducted in estrogen receptor-positive human breast cancer (MCF-7). Our results showed that xanthorrhizol significantly increased Gal-4/ER luciferase activity in a dose-dependent manner and induced the endogenous ER-estrogen response element (ERE) interaction in MCF-7 cells. Xanthorrhizol also significantly enhanced the expression of the pS2 gene in MCF-7 cells. In contrast, treatment using ICI 182780, an ER antagonist, suppressed all activities induced by xanthorrhizol, indicating ER-dependant activities were involved. These results suggest that xanthorrhizol possesses estrogenic activity and its estrogenic effects are mediated by estrogen-induced gene expression.
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PMID:Estrogenic activity of xanthorrhizol isolated from curcuma xanthorrhiza ROXB. 1988 4