Heterogeneity of human glioblastoma: Glutathione-S-transferase and methylguanine-methyltransferase

Periodical: Cancer Investigation ISBN: 0735-7907  Number: 6  Language: English  Pages: 597-609

Authors:Juillerat-Jeanneret, L., Bernasconi, C. C., Bricod, C., Gros, S., Trepey, S., Benhattar, J., Janzer, R. C.

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Abstract
The DNA repair and detoxifying enzymes, O-6-methylguanine-DNA-methyltransferase (MGMT) and glutathione-S-transferase (GST), may be responsible of poor response to alkylating agents in glioblastoma treatment. The methylation of MGMT promoter and the expression of MGMT and GST were highly heterogeneous in surgical specimens of human glioblastoma and in established human glioblastoma cells under 2-D and 3-D culture conditions, suggesting an intrinsic property of these cells. MGMT and GST expression did not predict the sensitivity of glioblastoma cells to alkylating agents. Combination of alkylating agents with inhibitors of GST disclosed additive effects, suggesting that inhibition of GST should be considered in glioblastoma therapy.