PMID: 9525814Apr 3, 1998Paper

Mechanism of action of lonidamine in the 9L brain tumor model involves inhibition of lactate efflux and intracellular acidification

Journal of Neuro-oncology
O Ben-YosephB D Ross

Abstract

Malignant gliomas have been associated with a high rate of glycolytic activity which is believed necessary to sustain cellular function and integrity. Since lonidamine (LND) is believed to reduce tumor glucose utilization by inhibition of the mitochondrially-bound glycolytic enzyme hexokinase (HK), 31P magnetic resonance spectroscopy (MRS) was used to noninvasively follow the effects of LND on both tumor pH and the high-energy phosphate metabolites: ATP, phosphocreatine (PCr) and inorganic phosphate (Pi) in subcutaneous rat 9L gliosarcomas. 31P tumor spectra acquired in 5 min intervals pre- and post LND administration of 50 and 100 mg/kg, i.p. revealed an acidotic pH shift of -0.25 and -0.45 pH units, respectively within 30 min post administration. The ATP/Pi ratio of 9L tumors decreased to 40% of control and Pi levels increased to 280% of control over a 3 hr period. LND exerted no effect on tumor blood flow and mean arterial blood pressure. Brain and muscle metabolite levels and pH were also unaffected by LND. In vitro measurements of cultured 9L tumor cell intra- and extracellular lactate, pentose phosphate pathway (PPP) and hexokinase (HK) activities suggest that the mode of action of LND involves inhibition of lactate efflu...Continue Reading

Citations

Oct 2, 2015·BioMed Research International·Diana Cervantes-MadridAlfonso Dueñas-González
Mar 13, 2012·Journal of Bioenergetics and Biomembranes·Céline PinheiroFátima Baltazar
May 12, 2018·Current Cancer Drug Targets·A P AlvesC J Maia
Jul 12, 2005·Annual Review of Biomedical Engineering·Robert J Gillies, David L Morse
Sep 16, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Paola PapaldoPaolo Marolla
Dec 4, 2013·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Ronald Allen CossDennis B Leeper
Dec 22, 2012·Neuro-oncology·Vera Miranda-GonçalvesFátima Baltazar
Feb 24, 2001·The Journal of International Medical Research·P Dell'AntoneL Piergallini
Nov 1, 2013·Endocrine-related Cancer·Filipa Morais-SantosCéline Pinheiro
Nov 2, 2015·The Journal of Biological Chemistry·Lili GuoIan A Blair
Aug 10, 2019·Molecular Metabolism·Valéry L PayenPierre Sonveaux

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