CYP1A1 and CYP1B1 expressions in medulloblastoma cells are AhR-independent and have no direct link with resveratrol-induced differentiation and apoptosis

Resveratrol induces apoptosis and regulates CYP 1A1 and CYP 1B1 expression inhuman 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 CYP 1A1 selective inhibitor (alpha-naphthoflavone,(alpha-NF), selective CYP 1A1/1A2 inducer (beta-naphthoflavone, beta-NF) and their combination with resveratrol, respectively. The influences of those treatments on the expressions of CYP 1A1, 1A2 and 1B1 as well as the cell growth, differentiation and death were analyzed. It was found that neither a-NF nor beta-NF had any effect on cell growth. (alpha-NF inhibited resveratrol-induced CYP 1A1 expression without interfering cell differentiation and apoptosis. beta-NF could up-regulate resveratrol-induced CYP 1A1 expression but not enhance the anti-cancer effects of resveratrol. CYP 1A2 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 I I pairs of human medulloblastoma and noncancerous cerebellar tissues revealed that AhR was undetectable in either of them, whereas CYP 1A1 was expressed in cerebellum but down-regulated or diminished in their malignant counterparts. Our data suggest for the first time that CYP 1A1 and 1131 expressions in human medulloblastoma cells are AhR-independent and have no direct links with resveratrol-induced differentiation and apoptosis. Appearance of CYP I A I expression may reflect a more maturated status and a better prognosis of medulloblastomas. (c) 2005 Elsevier Ireland Ltd. All rights reserved.