Differential regulation of CYP1A1 and CYP1B1 expression in resveratrol-treated human medulloblastoma cells.
Resveratrol induces differentiation and Fas-independent apoptosis of medulloblastoma cells by a largely unknown mechanism. CYP1A1 and 1B1 are involved in resveratrol-mediated tumor suppression but their expression in medulloblastoma cells and their relevance to anti-medulloblastoma activity of resveratrol have not been described. The statuses of CYP1A1 and 1B1 in UW228-3 medulloblastoma cells without and with resveratrol treatments were elucidated in this study with ethoxyresorufin O-deethylation assay, followed by RT-PCR, immunocytochemical staining and Western blot hybridization. CYP1A1/1B1 enzymatic activity was low in UW228-3 cells but became several folds higher upon resveratrol treatments. CYP1A1 was undetectable and CYP1B1 was expressed in normally cultured cells. Accompanied by the increased fraction of apoptosis, enhanced CYP1A1 and downregulated CYP1B1 were observed in resveratrol-treated cells in time- and dose-related fashions. Our results demonstrate for the first time that in the medulloblastoma cell system, CYP1A1 upregulation is paralleled with resveratrol-induced differentiation and apoptosis, while CYP1B1 may not be an essential element in metabolic activation of resveratrol in those cells. CYP1A1 and 1B1 are resveratrol response genes and potential chemosensitive markers of medulloblastoma cells.
Liu
Jia
J
Cancer Institute, Laboratory of Cell Biology and Molecular Genetics, College of Basic Medical Sciences, Dalian Medical University, Dalian 116027, PR China.
Wang
Qian
Q
Wu
Da-Chang
DC
Wang
Xiao-Wei
XW
Sun
Yuan
Y
Chen
Xiao-Yan
XY
Zhang
Kai-Li
KL
Li
Hong
H
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein; D005434:Flow Cytometry / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008527:Medulloblastoma; D008562:Membrane Glycoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors; D019014:fas Receptor / 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; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D000077185:Resveratrol