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  • Title: Curcumin down-regulates Ets-1 and Bcl-2 expression in human endometrial carcinoma HEC-1-A cells.
    Author: Yu Z, Shah DM.
    Journal: Gynecol Oncol; 2007 Sep; 106(3):541-8. PubMed ID: 17590421.
    Abstract:
    OBJECTIVE: Curcumin has been demonstrated to have an anti-tumor activity but the underlying molecular mechanisms are not fully uncovered. The present study was undertaken to determine the effect of curcumin on the expression of the proto-oncogene Ets-1 and the anti-apoptotic molecule Bcl-2 in human endometrial adenocarcinoma HEC-1-A cells. METHODS: Confluent HEC-1-A cells were treated with curcumin at various doses for 16 h or at 60 microM for various time points. At the end of the designated treatments, changes in cell morphology, DNA fragmentation and protein contents of Ets-1 and Bcl-2 were determined, respectively, by light microscopy, DNA laddering assay and Western blot analysis. As an initial step towards understanding whether Ets-1 was a possible up-stream regulator of Bcl-2 expression in HEC-1-A cells and if so, whether curcumin could attenuate the Ets-1-induced up-regulation of Bcl-2 expression, cells were transiently transfected with an Ets-1/GFP (Green Fluorescence Protein) fusion construct and the transfectants were treated with 60 microM curcumin for 16 h, followed by whole cell lysate preparation for Western blot analysis of Bcl-2 protein contents. RESULTS: Curcumin induced apoptosis-like morphological changes and DNA degradation and decreased basal levels of Ets-1 and Bcl-2 protein contents in HEC-1-A cells in a time- and dose-dependent manner. Overexpression of Ets-1 in the cell resulted in an increase in Bcl-2 protein contents and that increase was attenuated by curcumin treatment. CONCLUSIONS: Curcumin down-regulates Ets-1 and Bcl-2 expression and induces apoptosis in HEC-1-A cells, suggesting a novel molecular mechanism for the anti-tumor activity of curcumin.
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