The grape and wine constituent piceatannol inhibits proliferation of human bladder cancer cells via blocking cell cycle progression and inducing Fas/membrane bound Fas ligand-mediated apoptotic pathway.
Piceatannol (3,3',4,5'-Tetrahydroxy-trans-stilbene) is a polyphenol present in grapes and wine. Piceatannol is a protein kinase inhibitor that modifies multiple cellular targets exerting immunosuppressive, antileukemic, and antitumorigenic activities in several cell lines and animal models. In this study, the antiproliferative activity of piceatannol was investigated. The results showed that piceatannol inhibited the proliferation of T24 and HT1376 human bladder cancer cells by blocking cell cycle progression in the G0/G1 phase and inducing apoptosis. ELISA showed that the G0/G1 phase arrest is due to an increased in the expression of p21/WAF1. An enhancement in Fas/APO-1 and membrane-bound Fas ligand (mFasL) might be responsible for the apoptotic effect induced by piceatannol. Our study reports the novel finding, that the induction of p21/WAF1 and activity of the Fas/mFasL apoptotic system may participate in the antiproliferative activity of piceatannol in T24 and HT1376 cells.
Kuo
Po-Lin
PL
Cell Biology Laboratory, Department of Biotechnology, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.
Hsu
Ya-Ling
YL
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D053222:Fas Ligand Protein / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013267:Stilbenes / Q000302:isolation & purification / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000473:pathology*; D027843:Vitis; D014920:Wine
D053222:Fas Ligand Protein; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; C041525:3,3',4,5'-tetrahydroxystilbene; D011505:Protein-Tyrosine Kinases