Mechanism of Action of the Antineoplastic Drug Lonidamine: 31P and 13C Nuclear Magnetic Resonance Studies

摘要: The mechanism of action the antineoplastic drug lonidamine (LND) on MCF-7 human breast cancer cells was studied with use 31P and 13C nuclear magnetic resonance (NMR) spectroscopy. were embedded in alginate microcapsules, perfused growth media LND at physiological conditions NMR tube, continuously monitored vivo for effects LND. demonstrated intracellular acidification after perfusion concomitant ATP depletion changes phospholipid metabolites. showed marked LND-induced accumulation lactate, spectra perfusate disclosed that inhibited lactate transport. Kinetic also furnished information glucose metabolism; decreased initial uptake formation, although final levels higher compared those controls. Combined administration metabolic inhibitor 2-deoxyglucose yielded additive but not synergistic cytotoxicity enabled assessment hexokinase activity. Overall, results indicate major induced by are inhibition transport its accumulation, which lead to acidification.