Resveratrol Inhibits IL-6-Induced Transcriptional Activity of AR and STAT3 in Human Prostate Cancer LNCaP-FGC Cells.
10.4062/biomolther.2014.061
- Author:
Mee Hyun LEE
1
;
Joydeb Kumar KUNDU
;
Young Sam KEUM
;
Yong Yeon CHO
;
Young Joon SURH
;
Bu Young CHOI
Author Information
1. Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
- Publication Type:Original Article
- Keywords:
Resveratrol;
AR transcriptional activity;
STAT3 transcriptional activity;
Prostate cancer
- MeSH:
Dihydrotestosterone;
Genes, Reporter;
Humans;
Interleukin-6;
Prostate;
Prostate-Specific Antigen;
Prostatic Neoplasms*;
Receptors, Androgen;
Transducers;
Vitis
- From:Biomolecules & Therapeutics
2014;22(5):426-430
- CountryRepublic of Korea
- Language:English
-
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.
