title: Resveratrol Inhibits IL-6-Induced Transcriptional Activity of AR and STAT3 in Human Prostate Cancer LNCaP-FGC Cells.
abstract: Prostate cancer is the most frequently diagnosed cancer. Although prostate tumors respond to androgen ablation therapy at an early stage, they often acquire the potential of androgen-independent growth. Elevated transcriptional activity of androgen receptor (AR) and/or signal transducer and activator of transcription-3 (STAT3) contributes to the proliferation of prostate cancer cells. In the present study, we examined the effect of resveratrol, a phytoalexin present in grapes, on the reporter gene activity of AR and STAT3 in human prostate cancer (LNCaP-FGC) cells stimulated with interleukin-6 (IL-6) and/or dihydrotestosterone (DHT). Our study revealed that resveratrol suppressed the growth of LNCaP-FGC cells in a time- and concentration-dependent manner. Whereas the AR transcriptional activity was induced by treatment with either IL-6 or DHT, the STAT3 transcriptional activity was induced only by treatment with IL-6 but not with DHT. Resveratrol significantly attenuated IL-6-induced STAT3 transcriptional activity, and DHT- or IL-6-induced AR transcriptional activity. Treatment of cells with DHT plus IL-6 significantly increased the AR transcriptional activity as compared to DHT or IL-6 treatment alone and resveratrol markedly diminished DHT plus IL-6-induced AR transcriptional activity. Furthermore, the production of prostate-specific antigen (PSA) was decreased by resveratrol in the DHT-, IL-6- or DHT plus IL-6-treated LNCaP-FGC cells. Taken together, the inhibitory effects of resveratrol on IL-6- and/or DHT-induced AR transcriptional activity in LNCaP prostate cancer cells are partly mediated through the suppression of STAT3 reporter gene activity, suggesting that resveratrol may be a promising therapeutic choice for the treatment of prostate cancer.
authors.affiliation: Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742 ; College of Pharmacy, The Catholic University of Korea, Bucheon 420-743.
authors.forename: Mee-Hyun
authors.initials: MH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Keimyung University, Daegu 704-701.
authors.forename: Joydeb Kumar
authors.initials: JK
authors.lastname: Kundu
authors.affiliation: College of Pharmacy, Dongguk University, Goyang 410-820.
authors.forename: Young-Sam
authors.initials: YS
authors.lastname: Keum
authors.affiliation: College of Pharmacy, The Catholic University of Korea, Bucheon 420-743.
authors.forename: Yong-Yeon
authors.initials: YY
authors.lastname: Cho
authors.affiliation: Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742.
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Surh
authors.affiliation: Pharmaceutical Science and Engineering, School of Convergence Bioscience and Technology, Seowon University, Cheongju 361-742, Republic of Korea.
authors.forename: Bu Young
authors.initials: BY
authors.lastname: Choi
keywords: AR transcriptional activity; Prostate cancer; Resveratrol; STAT3 transcriptional activity