Investigating a signature of temozolomide resistance in GBM cell lines using metabolomics

  1. Get@NRC: Investigating a signature of temozolomide resistance in GBM cell lines using metabolomics (Opens in a new window)
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Journal titleJournal of Neuro-Oncology
Pages91102; # of pages: 12
Subjectaconitic acid; adenosine; alanine; arginine; choline; citric acid; creatine; glucose; glutamic acid; glutamine; glutathione; glycerophosphate; histidine; inositol; isocitric acid; isoleucine; leucine; lomeguatrib; methionine; methylated DNA protein cysteine methyltransferase; phosphorylcholine; proline; serine; succinic acid; taurine; temozolomide; threonine; tryptophan; unindexed drug; valine; amino acid metabolism; antineoplastic activity; cancer cell line; cancer resistance; cell viability; citric acid cycle; concentration response; controlled study; cytotoxicity; down regulation; drug sensitivity; enzyme inhibition; genetic transcription; glioblastoma; glioblastoma multiforme cell line; glycolysis; human cell; human tissue; metabolite; metabolomics; primary tumor; upregulation
AbstractGlioblastoma multiforme (GBM) is the most common form of malignant glioma. Current therapeutic approach to treat this malignancy involves a combination of surgery, radiotherapy and chemotherapy with temozolomide. Numerous mechanisms contributing to inherent and acquired resistance to this chemotherapeutic agent have been identified and can lead to treatment failure. This study undertook a metabolomics-based approach to characterize the metabolic profiles observed in temozolomide-sensitive and temozolomide-resistant GBM cell lines as well as in a small sub-set of primary GBM tumors. This approach was also utilized to explore the metabolic changes modulated upon cell treatment with temozolomide and lomeguatrib, an MGMT inhibitor with temozolomide-sensitizing potential. Metabolites previously explored for their potential role in chemoresistance including glucose, citrate and isocitrate demonstrated elevated levels in temozolomide-resistant GBM cells. In addition, a signature of metabolites comprising alanine, choline, creatine and phosphorylcholine was identified as up-regulated in sensitive GBM cell line across different treatments. These results present the metabolic profiles associated with temozolomide response in selected GBM models and propose interesting leads that could be leveraged for the development of therapeutic or diagnostic tools to impact temozolomide response in GBMs.
Publication date
PublisherSpringer International Publishing
AffiliationNational Research Council Canada; Information and Communication Technologies
Peer reviewedYes
NPARC number21276985
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Record identifierf46dfba2-3983-4ffd-8307-a73e2c6cb594
Record created2015-11-10
Record modified2016-05-09
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