title: CYP1A1 and CYP1B1 expressions in medulloblastoma cells are AhR-independent and have no direct link with resveratrol-induced differentiation and apoptosis.
abstract: Resveratrol induces apoptosis and regulates CYP1A1 and CYP1B1 expression in human medulloblastoma cells. To elucidate the potential correlation of their expressions with the anti-medulloblastoma effects of resveratrol, human medulloblastoma cells, UW228-3, were treated with CYP1A1 selective inhibitor (alpha-naphthoflavone, alpha-NF), selective CYP1A1/1A2 inducer (beta-naphthoflavone, beta-NF) and their combination with resveratrol, respectively. The influences of those treatments on the expressions of CYP1A1, 1A2 and 1B1 as well as the cell growth, differentiation and death were analyzed. It was found that neither alpha-NF nor beta-NF had any effect on cell growth. alpha-NF inhibited resveratrol-induced CYP1A1 expression without interfering cell differentiation and apoptosis. beta-NF could up-regulate resveratrol-induced CYP1A1 expression but not enhance the anti-cancer effects of resveratrol. CYP1A2 was undetectable in the cells irrespective to the treatments. Aryl hydrocarbon receptor (AhR) was absent in UW228-3 cells under normal culture and treated with resveratrol but induced by both alpha- and beta-NF. Immunohistochemical examination performed on 11 pairs of human medulloblastoma and noncancerous cerebellar tissues revealed that AhR was undetectable in either of them, whereas CYP1A1 was expressed in cerebellum but down-regulated or diminished in their malignant counterparts. Our data suggest for the first time that CYP1A1 and 1B1 expressions in human medulloblastoma cells are AhR-independent and have no direct links with resveratrol-induced differentiation and apoptosis. Appearance of CYP1A1 expression may reflect a more maturated status and a better prognosis of medulloblastomas.
authors.affiliation: Cancer Institute and Liaoning Laboratory of Cancer Genomics, College of Basic Medical Sciences, Dalian Medical University, Zhanshan Road 465, 6027 Dalian, PR China.
authors.forename: Mo-Li
authors.initials: ML
authors.lastname: Wu
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Da-Chang
authors.initials: DC
authors.lastname: Wu
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Wang
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Chen
authors.forename: Qing-You
authors.initials: QY
authors.lastname: Kong
authors.forename: Jing-Xin
authors.initials: JX
authors.lastname: Ma
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D065633:Cytochrome P-450 CYP1B1; D004338:Drug Combinations; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008527:Medulloblastoma; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D018336:Receptors, Aryl Hydrocarbon; D013267:Stilbenes; D016708:Synaptophysin; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D000077185:Resveratrol