Growth-stimulatory effect of resveratrol in human cancer cells.
Earlier studies have shown that resveratrol could induce death in several human cancer cell lines in culture. Here we report our observation that resveratrol can also promote the growth of certain human cancer cells when they are grown either in culture or in athymic nude mice as xenografts. At relatively low concentrations (</=5 microM), resveratrol exerted a significant growth-stimulatory effect in the MDA-MB-435s human cancer cells, but this effect was not observed in several other human cell lines tested. Analysis of cell signaling molecules showed that resveratrol induced the activation of JNK, p38, Akt, and NF-kappaB signaling pathways in these cells. Further analysis using pharmacological inhibitors showed that only the NF-kappaB inhibitor (BAY11-7082) abrogated the growth-stimulatory effect of resveratrol in cultured cells. In athymic nude mice, resveratrol at 16.5 mg/kg body weight enhanced the growth of MDA-MB-435s xenografts compared to the control group, while resveratrol at the 33 mg/kg body weight dose did not have a similar effect. Additional analyses confirmed that resveratrol stimulated cancer cell growth in vivo through activation of the NF-kappaB signaling pathway. Taken together, these observations suggest that resveratrol at low concentrations could stimulate the growth of certain types of human cancer cells in vivo. This cell type-specific mitogenic effect of resveratrol may also partly contribute to the procarcinogenic effect of alcohol consumption (rich in resveratrol) in the development of certain human cancers.
Fukui
Masayuki
M
Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Yamabe
Noriko
N
Kang
Ki Sung
KS
Zhu
Bao Ting
BT
D000818:Animals; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D009369:Neoplasms / Q000235:genetics; D009423:Nervous System Neoplasms / Q000235:genetics; D009570:Nitriles; D010636:Phenols / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013267:Stilbenes / Q000494:pharmacology*; D013450:Sulfones
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D016328:NF-kappa B; D009570:Nitriles; D010636:Phenols; D013267:Stilbenes; D013450:Sulfones; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol