|Hudson, Tamaro - NCI|
|Wang, Tien-Chung - UNIV. OF MARYLAND|
|Kim, Young - NCI|
|Seifried, Harold - NIC|
|Perkins, Susan - UNIV. OF TEXAS|
|Hursting, Stephen - UNIV. OF TEXAS|
Submitted to: Carcinogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 29, 2008
Publication Date: June 26, 2008
Citation: Wang, T.T., Hudson, T.S., Wang, T.C., Remsberg, C.M., Davies, N.M., Takahashi, Y., Kim, Y.S., Seifried, H., Vinyard, B.T., Perkins, S.N., Hursting, S.D. 2008. Differential effects of resveratrol on androgen-responsive LNCaP human prostrate cancer cells in vitro and in vivo. Carcinogenesis. 29(10):2001-2010. Interpretive Summary: Resveratrol is a phytochemical that has been under consideration for use as a prostate cancer preventive agent. However, the efficacy, as well as the mechanisms of action of resveratrol on prostate cancer prevention, remains largely unknown. This study seeks to address these questions and examine the cancer preventive effects of resveratrol using a complementary LNCaP cell culture (in vitro) and xenograft (in vivo) models. We found resveratrol to be effective in inhibiting prostate cancer cell growth in vivo and in vitro. The effects of resveratrol are associated with modulation of multiple pathways including steroid hormone-mediated events. However, exposure to resveratrol has also led to increased angiogenesis (growth of blood vessels) and inhibition of apoptosis (programmed cell death) in the xenograft. These findings provide evidence for efficacy and mechanisms of resveratrol’s effects in prostate cancer cells in vivo and in vitro and lay the foundation for elucidating the mechanisms of resveratrol’s biological impact in prostate cancer cells. This work provides novel information for cancer research scientists regarding molecular targets and mechanism(s) of action of resveratrol and will serve as an important basis for future design of cancer preventive strategy.
Technical Abstract: Resveratrol is a phytochemical that has been under consideration for use as a prostate cancer chemopreventive agent. However, the efficacy, as well as the mechanisms of action of resveratrol on prostate cancer prevention, remains largely unknown. This study seeks to address these questions and examine the cancer preventive effects of resveratrol using a complementary LNCaP cell culture and xenograft models. In cultured LNCaP cells, we found that resveratrol inhibited cell growth. The growth inhibitory effects of resveratrol appeared to be through modulation of both androgen and estrogen-mediated events. Global gene expression analysis using microarrays identified androgen-responsive genes as a group of genes universally affected by resveratrol in LNCaP cells in vitro. The effect of resveratrol on expression of these genes appeared to be through inhibition of both androgen and estrogen-mediated transcription. In a xenograft model, resveratrol delayed tumor growth and inhibited expression of a marker for steroid hormone responses. However, exposure to resveratrol also led to increased angiogenesis and inhibition of apoptosis in the xenograft. In summary, resveratrol may act through modulation of steroid hormone-dependent pathways to inhibit prostate cancer cell growth in both culture and xenografts, but exposure in vivo may be of concern.