title: Identification of a potent inhibitor targeting human lactate dehydrogenase A and its metabolic modulation for cancer cell line.
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.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400030, PR China. Electronic address: chunyechen713@gmail.com.
authors.forename: Chun-Ye
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Deng
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D061986:MCF-7 Cells; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5
keywords: Cytotoxic assay; Enzymatic assay; Lactate dehydrogenase A; Virtual screening