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Brain Sci. 2018, 8(4), 56; https://doi.org/10.3390/brainsci8040056

Oxamate, but Not Selective Targeting of LDH-A, Inhibits Medulloblastoma Cell Glycolysis, Growth and Motility

Cellular & Molecular Neuro-oncology Research Group, University of Portsmouth, School of Pharmacy & Biomedical Sciences, Portsmouth PO1 2DT, UK
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Received: 14 January 2018 / Revised: 16 March 2018 / Accepted: 28 March 2018 / Published: 30 March 2018
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Abstract

Medulloblastoma is the most common malignant paediatric brain tumour and current therapies often leave patients with severe neurological disabilities. Four major molecular groups of medulloblastoma have been identified (Wnt, Shh, Group 3 and Group 4), which include additional, recently defined subgroups with different prognosis and genetic characteristics. Lactate dehydrogenase A (LDHA) is a key enzyme in the aerobic glycolysis pathway, an abnormal metabolic pathway commonly observed in cancers, associated with tumour progression and metastasis. Studies indicate MBs have a glycolytic phenotype; however, LDHA has not yet been explored as a therapeutic target for medulloblastoma. LDHA expression was examined in medulloblastoma subgroups and cell lines. The effects of LDHA inhibition by oxamate or LDHA siRNA on medulloblastoma cell line metabolism, migration and proliferation were examined. LDHA was significantly overexpressed in Group 3 and Wnt MBs compared to non-neoplastic cerebellum. Furthermore, we found that oxamate significantly attenuated glycolysis, proliferation and motility in medulloblastoma cell lines, but LDHA siRNA did not. We established that aerobic glycolysis is a potential therapeutic target for medulloblastoma, but broader LDH inhibition (LDHA, B, and C) may be more appropriate than LDHA inhibition alone. View Full-Text
Keywords: LDHA; lactate dehydrogenase; medulloblastoma; aerobic glycolysis; Warburg effect; oxamate LDHA; lactate dehydrogenase; medulloblastoma; aerobic glycolysis; Warburg effect; oxamate
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Valvona, C.J.; Fillmore, H.L. Oxamate, but Not Selective Targeting of LDH-A, Inhibits Medulloblastoma Cell Glycolysis, Growth and Motility. Brain Sci. 2018, 8, 56.

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