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* To whom correspondence should be addressed. E-mail: hhj143{at}mail.cgu.edu.tw.
Curcumin, a naturally occurring compound, exhibits anti-cancer chemopreventive effects. We evaluated the effects and mechanisms of curcumin on the gene expression of prostate-specific antigen (PSA) in human androgen-sensitive prostatic carcinoma cells. LNCaP cells were used to determine the effect of curcumin on PSA expression. Quantitative PSA expressions were assessed using RT-PCR, enzyme linked immunosorbent assay (ELISA), and immunoblot assay. The modulation of androgen, interlukin-6 (IL-6) and prostate-derived Ets factor (PDEF) on PSA gene was identified by transient gene expression assay using a PSA reporter vector. The effect of curcumin on the activity of androgen receptor was evaluated using electrophoretic mobility shift assay (EMSA). Immunoblot assays, RT-PCR, and ELISA indicated that curcumin treatments blocked the stimulation of methyltrienolone (R1881) and IL-6 on PSA gene expression in LNCaP cells. The effects of curcumin appear to be mediated via the androgen response element of PSA gene. Results from immunoblot assay and EMSA revealed the modulation of curcumin on the expression of androgen receptor and androgen receptor binding activity on androgen response element of PSA gene. Although overexpression of PDEF dramatically enhanced PSA gene expression, the results of immunoblot assays and transient reporter assays indicated that curcumin treatments did not affect the gene expression of PDEF. Curcumin inhibits R1881- and IL-6-mediated expression of PSA gene expression in LNCaP cells through the downregulation of the expression and activity of androgen receptor.
Key words: Androgen
Prostate
PDEF
PSA
androgen receptor
curcumin
interlukin-6
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