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See Latest ArticlesIndoleamine 2,3-dioxygenase as a new target for malignant glioma therapy
Journal of Neurosurgery, 08/13/09
Miyazaki T et al. – In a study to investigate the possibility of indoleamine 2,3-dioxygenase (IDO)-dependent tryptophan (Trp) depletion by malignant gliomas and the practicability of using an IDO inhibitor with anticancer drugs to reserve Trp without decreasing cytotoxicity of the drugs, the findings suggest that robust IDO expression with rapid consumption of Trp in human glioma cells induced by interferon-γ (IFN-γ) could lead to immune resistance in glioma cells. IDO inhibitors that prevent Trp depletion could be used with anticancer drugs to improve therapeutic effects.
Methods- Expression of IDO and other KP enzymes and effects of an IDO inhibitor, 1-methyl L-tryptophan (1MT), on Trp metabolism and cytotoxicity of anticancer drugs was studied, together with direct measurement of KP metabolites, in cultured human malignant glioma cells.
- Upon IFN-γ stimulation, glioma cells greatly increased their IDO mRNA expression concomitant with depletion of Trp.
- IDO inhibitor 1MT successfully prevented Trp consumption by the stimulated glioma cells.
- Combining 1MT with anticancer drugs (temozolomide, bischloroethylnitrosourea [BCNU], etoposide and cisplatin) did not interfere with the drugs' suppression of growth of LN229 glioma cells but rather increased their inhibitory effects on IDO activity.
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