Curcumin blocks the activation of androgen and interlukin-6 on prostate-specific antigen expression in human prostatic carcinoma cells.
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.
Tsui
Ke-Hung
KH
Department of Urology, Chang Gung Memorial Hospital, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan, Republic of China.
Feng
Tsui-Hsia
TH
Lin
Chang-Mei
CM
Chang
Phei-Lang
PL
Juang
Horng-Heng
HH
D000728:Androgens / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D017430:Prostate-Specific Antigen / Q000096:biosynthesis / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets / Q000096:biosynthesis / Q000187:drug effects; D011944:Receptors, Androgen / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D000728:Androgens; D000970:Antineoplastic Agents; D015850:Interleukin-6; D050783:Proto-Oncogene Proteins c-ets; D011944:Receptors, Androgen; C403974:SPDEF protein, human; D017430:Prostate-Specific Antigen; D003474:Curcumin