Resveratrol promotes differentiation and induces Fas-independent apoptosis of human medulloblastoma cells.
Resveratrol has tumor-suppressive activities in some in vitro and in vivo experimental systems but its effect on medulloblastoma cells is still unknown. In this study, resveratrol was used to treat four human medulloblastoma cell lines (Med-3, UW228-1, -2 and -3) and its effects on cell growth, differentiation and death were examined by multiple approaches. Expression of Fas, FasL and caspase-3 in the cells without and with resveratrol treatments was examined by immunocytochemical staining and mRNA in situ hybridization and the influence of anti-Fas antibody (200 ng/ml) in cell growth and survival was determined as well. The results demonstrated that resveratrol could suppress growth, promote differentiation and commit its target cells to apoptosis in time- and dose-related fashions. Fas was constitutively expressed but FasL was undetectable in the four lines in spite of resveratrol treatment. Anti-Fas antibody (200 ng/ml) neither inhibited growth nor induced apoptosis of those cell lines. Up-regulated caspase-3 was found in resveratrol-treated populations and appearance of its cleaved form was closely associated with the apoptotic event. These findings suggest for the first time that resveratrol is an effective anti-medulloblastoma agent that kills medulloblastoma cells through a Fas-independent pathway.
Wang
Qian
Q
Cancer Institute and Laboratory of Cell Biology and Molecular Genetics, College of Basic Medical Sciences, Dalian Medical University, 116027, Dalian, PR China.
Li
Hong
H
Wang
Xiao-Wei
XW
Wu
Da-chang
DC
Chen
Xiao-Yan
XY
Liu
Jia
J
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein; D006801:Humans; D008527:Medulloblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D019014:fas Receptor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D013267:Stilbenes; D019014:fas Receptor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000077185:Resveratrol