title: Targeting glycolysis in leukemia: a novel inhibitor 3-BrOP in combination with rapamycin.
abstract: Rapidly proliferating solid tumor cells are often dependent on glycolysis for ATP production even in normoxia (the Warburg effect), however it is not yet clear whether acute leukemias have a similarly increased dependence on aerobic glycolysis. We report that all acute leukemia subtypes (pre-B ALL, T-ALL and AML) demonstrated growth arrest and cell death when treated the novel glycolysis inhibitor 3-BrOP. Potentiated ATP depletion and pro-apoptotic effects were seen for 3-BrOP combinations with the cytochrome-c-reductase inhibitor antimycin A and the mTOR inhibitor rapamycin. These results reveal a potential role for glycolysis inhibition in acute leukemia subtypes and suggest potential combinations.
authors.affiliation: Cook Children's Hospital, Fort Worth, TX, USA.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Akers
authors.forename: Wendy
authors.initials: W
authors.lastname: Fang
authors.forename: Alejandro G
authors.initials: AG
authors.lastname: Levy
authors.forename: Anna R
authors.initials: AR
authors.lastname: Franklin
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Zweidler-McKay
mesh_terms: D000208:Acute Disease; D000255:Adenosine Triphosphate / Q000378:metabolism; D000968:Antimycin A / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006019:Glycolysis / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000494:pharmacology*; D015151:Immunoblotting; D019169:Jurkat Cells; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011422:Propionates / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology*; D013997:Time Factors; D020298:U937 Cells
chemical_list: C568307:3-bromo-2-oxopropionate-1-propyl ester; D006842:Hydrocarbons, Brominated; D011422:Propionates; D000968:Antimycin A; D000255:Adenosine Triphosphate; D053148:Caspase 3; D020123:Sirolimus