Abstract
Targeting LDHA represents a promising strategy for the development of new anti-cancer agents. We report herein the identification of a potent compound as a direct LDHA inhibitor. The in vitro enzymatic assay revealed that the VS-2 had good inhibitory potency (IC50=0.25μM) to LDHA. Cytotoxic assay suggested that the VS-2 could inhibit MCF-7 cancer cell growth, with the IC50 value low to 1.54μM. The seahorse XF24 experiment validated that the VS-2 served as a modulator to reprogram MCF-7 cancer cell metabolism from glycolysis to mitochondrial respiration.
Keywords:
Cytotoxic assay; Enzymatic assay; Lactate dehydrogenase A; Virtual screening.
Copyright © 2015 Elsevier Ltd. All rights reserved.
MeSH terms
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology*
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology*
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Glycolysis / drug effects
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Humans
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / metabolism
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L-Lactate Dehydrogenase / antagonists & inhibitors*
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L-Lactate Dehydrogenase / metabolism
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Lactate Dehydrogenase 5
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MCF-7 Cells
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Mitochondria / drug effects
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Mitochondria / metabolism
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Models, Molecular
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Molecular Structure
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Isoenzymes
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L-Lactate Dehydrogenase
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Lactate Dehydrogenase 5