Bcl-2 overexpression decreases BCNU sensitivity of a human glioblastoma line through enhancement of catalase activity

The aim of this study was to evaluate the role of bcl-2 in 1,3-bis(2-chloro ethyl)-1-nitrosourea (BCNU) sensitivity of the ADFS human glioblastoma cell line in vitro and in vivo. To this end, the ADFS line expressing a low lev el of the bcl-2 protein was transfected with a bcl-2 expression vector. We found that bcl-2 overexpressing clones were less sensitive to in vitro BCNU treatment than the control clone. Cell cycle analysis demonstrated that wh ile BCNU induced a consistent block in S/G2-M phases of the cell cycle in t he control clone, it did not affect the cell cycle phase distribution of th e two bcl-2 transfectants. The different sensitivity to BCNU was unrelated to the ability of bcl-2 to inhibit apoptosis, while bcl-2 appeared to prote ct bcl-2 transfectants from BCNU toxicity through an increase of catalase a ctivity. The ability of the catalase inhibitor, sodium azide, to increase t he BCNU sensitivity of the bcl-2 transfectants to levels of the BCNU-treate d control clone substantiated the role of the catalase activity. The effect of bcl-2 in reducing sensitivity to BCNU was also confirmed by in vivo exp eriments. Xenografts of bcl-2 overexpressing tumors were less sensitive to BCNU treatment than xenografts originating from control cells. J. Cell. Bio chem. 83: 473-483, 2001. (C) 2001 Wiley-Liss, Inc.