Resveratrol Inhibits IL-6-Induced Transcriptional Activity of AR and STAT3 in Human Prostate Cancer LNCaP-FGC Cells

Abstract

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. www.biomolther.orgProstate 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 DHTinduced 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.

Resveratrol suppresses the growth and metastatic potential of cervical cancer by inhibiting STAT3Tyr705 phosphorylation

“…STAT3 activity suppression induces the apoptosis of tumor cells 13,16,17 . RES inhibits the interleukin‐6 (IL‐6)‐induced transcriptional activity of STAT3 in human prostate cancer LNCaP‐FGC cells 18 and STAT3 axis in primary glioblastoma tumor‐initiating cells 19 . STAT3 signaling inhibition plays a critical role in the RES‐induced suppression of several cancer types, including ovarian cancer, 20,21 pancreatic cancer, 22 head and neck tumor, 23 osteosarcoma, 24 colorectal cancer, 25 and colon cancer 26 .…”

Molecular insights into phytochemicals‐driven break function in tumor microenvironment

“…When these cells are induced with IL‐6 then STAT3 transcriptional activity is enhances and when these cells are induced by DHT (dihydrotestosterone) or IL‐6 then it enhanced AR transcriptional activity. Both these transcriptional activities are reported to be attenuated by resveratrol (Lee et al., 2014). In melanoma TME, resveratrol was found to inhibit IL‐18 level which in turn reduces metastasis (Salado et al., 2011).…”

The Role of Resveratrol in Human Male Fertility

“…This suggests a possible role for RSV in male fertility. Furthermore, RSV seems to have a phytoestrogen activity in the androgen receptor (AR) by inhibiting its dimerization [ 21 ] and its IL-6 induced transcriptional activity [ 22 ] in prostate cancer cells. In testis, the activity of RSV may involve some transcription factors that affect the function of the AR [ 23 ].…”