Troglitazone reduces glyoxalase I protein expression in glioma and potentiates the effects of chemotherapeutic agents.
Despite resistance of most gliomas to chemotherapy, approximately 2/3 of oligodendrogliomas show sensitivity to such agents. This sensitivity has been associated with deletions on chromosome 1p alone or in combination with 19q. Higher expression of the enzyme glyoxalase I has been found in oligodendrogliomas with chromosome 1p intact compared to those with a deletion. Higher expression of this enzyme is also associated with tumor chemoresistance in other cancers. The present study tested whether the drug troglitazone would make a glioma cell line more sensitive to chemotherapeutic agents. This drug was chosen because it has been shown to decrease glyoxalase I enzyme activity in cells. Treatment with troglitazone decreased expression of glyoxalase I, and potentiated cell death when used in combination with chemotherapeutic agents. This decrease in glyoxalase I protein may be one mechanism by which this potentiation occurs, and troglitazone may be a candidate for use in glioma therapy.
Helgager
Jeffrey
J
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1414, USA.
Li
Jie
J
Lubensky
Irina A
IA
Lonser
Russell
R
Zhuang
Zhengping
Z
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