Apurinic endonuclease (Ape1/Ref-1) contributes to glioma cell line alkylator resistance

Silber, J.R., Bobola, M.S., Blank, A., Schoeler, K.D., Haroldson, P.D., Huynh, M.B. and Kolstoe, D.D.The apurinic/apyrimidinic endonuclease activity of Ape1/Ref-1 contributes to human glioma cell resistance to alkylating agents and is elevated by oxidative stress. Clin. Cancer Res. 8: 3008-3018, 2002

Antisense suppression of Ape1/Ref-1 reduces resistance to temozolomide and increases abasic site abundance. Antisense (ASO)-mediated suppression of Ape1/Ref-1 level increased sensitivity of human glioma cells (SNB19) to temozolomide (left panel) and BCNU (not shown). Increased cytotoxicity was accompanied by increased abundance of abasic sites, indicating that suppression of the apurinic endonuclease activity of Ape1/Ref-1 was responsible for potentiating alkylator cytotoxicity. Red, antisense-treated cells.