Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines.
Curcumin, traditionally used as a seasoning spice in Indian cuisine, has been reported to decrease the proliferation potential of prostate cancer cells, by a mechanism that is not fully understood. In the current study, we have evaluated the effects of curcumin in cell growth, activation of signal transduction, and transforming activities of both androgen-dependent and independent cell lines. Prostate cancer cell lines, LNCaP and PC-3, were treated with curcumin and its effects were further analyzed on signal transduction and expression of androgen receptor (AR) and AR-related cofactors using transient transfection assay and Western blotting. Our results show that curcumin down-regulates transactivation and expression of AR, activator protein-1 (AP-1), nuclear factor-kappaB (NF-kappaB), and CREB (cAMP response element-binding protein)-binding protein (CBP). Curcumin also inhibited the transforming activities of both cell lines as evidenced by the reduced colony forming ability in soft agar. The results obtained here demonstrate that curcumin has a potential therapeutic effect on prostate cancer cells through down-regulation of AR and AR-related cofactors (AP-1, NF-kappaB and CBP).
Nakamura
Keiichiro
K
Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Yasunaga
Yutaka
Y
Segawa
Takehiko
T
Ko
Daejin
D
Moul
Judd W
JW
Srivastava
Shiv
S
Rhim
Johng S
JS
D000970:Antineoplastic Agents / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016328:NF-kappa B; D011944:Receptors, Androgen; D018808:Transcription Factor AP-1; D003474:Curcumin