Published-Ahead-of-Print July 31, 2008, DOI:10.2164/jandrol.108.004911
Journal of Andrology, Vol. 29, No. 6, November/December 2008
Copyright © American Society of Andrology
DOI: 10.2164/jandrol.108.004911
Curcumin Blocks the Activation of Androgen and Interlukin-6 on Prostate-Specific Antigen Expression in Human Prostatic Carcinoma Cells
KE-HUNG TSUI*,
,
TSUI-HSIA FENG
,
CHANG-MEI LIN
,
PHEI-LANG CHANG* AND
HORNG-HENG JUANG
,
From the * Department of Urology and the
Molecular Image Center, Chang Gung Memorial
Hospital, and the
School of Nursing and the
Department of Anatomy, Chang Gung University,
Kwei-Shan, Tao-Yuan, Taiwan, Republic of China.
|
Correspondence to: Dr Horng-Heng Juang, Department of Anatomy, Chang Gung
University, 259 Wen-Hua 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan, Republic of
China (e-mail:
hhj143{at}mail.cgu.edu.tw). |
Curcumin, a naturally occurring compound, exhibits anticancer
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
expression was assessed by reverse transcription polymerase chain reaction
(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 the PSA gene was identified by transient gene expression assay with
the use of a PSA reporter vector. The effect of curcumin on the activity of
androgen receptors was evaluated by 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 PSA gene expression in LNCaP
cells through down-regulation of the expression and activity of androgen
receptors.
Key words: IL-6, androgen receptor, PSA, PDEF, R1881
Copyright © 2008 by The American Society of Andrology.