Differential effects of resveratrol on androgen-responsive LNCaP human prostate cancer cells in vitro and in vivo.
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 complementary human LNCaP prostate cancer 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 LNCaP 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.
Wang
Thomas T Y
TT
Diet, Genomics and Immunology Laboratory, Beltsville Human Nutrition Research Center, United States Department of Agriculture, 10300 Baltimore Avenue, Beltsville, MD 20705, USA. tom.wang@ars.usda.gov
Hudson
Tamaro S
TS
Wang
Tien-Chung
TC
Remsberg
Connie M
CM
Davies
Neal M
NM
Takahashi
Yoko
Y
Kim
Young S
YS
Seifried
Harold
H
Vinyard
Bryan T
BT
Perkins
Susan N
SN
Hursting
Stephen D
SD
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017526:Receptor, IGF Type 1 / Q000235:genetics; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D000728:Androgens; D016588:Anticarcinogenic Agents; D013267:Stilbenes; D015741:Metribolone; D004958:Estradiol; D017526:Receptor, IGF Type 1; D000077185:Resveratrol