Changes in pyruvate metabolism detected by magnetic resonance imaging are linked to DNA damage and serve as a sensor of temozolomide response in glioblastoma cells

• Published in: Cancer research (Chicago, Ill.) Vol. 74; no. 23; pp. 7115 - 7124
• Main Authors: Park, Ilwoo, Mukherjee, Joydeep, Ito, Motokazu, Chaumeil, Myriam M, Jalbert, Llewellyn E, Gaensler, Karin, Ronen, Sabrina M, Nelson, Sarah J, Pieper, Russell O
• Format: Journal Article
• Language: English
• Published: United States 01.12.2014
• Subjects: Apoptosis - drug effects; Apoptosis - genetics; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Line, Tumor; Checkpoint Kinase 1; Dacarbazine - analogs & derivatives; Dacarbazine - pharmacology; DNA Damage - physiology; DNA Repair; Gene Expression - drug effects; Glioblastoma - drug therapy; Glioblastoma - genetics; Glioblastoma - metabolism; Humans; L-Lactate Dehydrogenase - genetics; L-Lactate Dehydrogenase - metabolism; Magnetic Resonance Imaging - methods; Membrane Proteins - genetics; Membrane Proteins - metabolism; Methyltransferases - genetics; Methyltransferases - metabolism; NAD - genetics; NAD - metabolism; Protein Kinases - genetics; Protein Kinases - metabolism; Pyruvic Acid - metabolism; Temozolomide; Thyroid Hormone-Binding Proteins; Thyroid Hormones - genetics; Thyroid Hormones - metabolism

Recent findings show that exposure to temozolomide (TMZ), a DNA-damaging drug used to treat glioblastoma (GBM), can suppress the conversion of pyruvate to lactate. To understand the mechanistic basis for this effect and its potential utility as a TMZ response biomarker, we compared the response of i...