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‐chloroethyl)‐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 level 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 while BCNU induced a consistent block in S/G2‐M phases of the cell cycle in the control clone, it did not affect the cell cycle phase distribution of the 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 protect bcl‐2 transfectants from BCNU toxicity through an increase of catalase activity. The ability of the catalase inhibitor, sodium azide, to increase the BCNU sensitivity of the bcl‐2 transfectants to levels of the BCNU‐treated 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 experiments. Xenografts of bcl‐2 overexpressing tumors were less sensitive to BCNU treatment than xenografts originating from control cells. J. Cell. Biochem. 83: 473–483, 2001. © 2001 Wiley‐Liss, Inc.