title: Characterization of a novel metabolic strategy used by drug-resistant tumor cells.
abstract: Acquired or inherent drug resistance is the major problem in achieving successful cancer treatment. However, the mechanism(s) of pleiotropic drug resistance remains obscure. We have identified and characterized a cellular metabolic strategy that differentiates drug-resistant cells from drug-sensitive cells. This strategy may serve to protect drug-resistant cells from damage caused by chemotherapeutic agents and radiation. We show that drug-resistant cells have low mitochondrial membrane potential, use nonglucose carbon sources (fatty acids) for mitochondrial oxygen consumption when glucose becomes limited, and are protected from exogenous stress such as radiation. In addition, drug-resistant cells express high levels of mitochondrial uncoupling protein 2 (UCP2). The discovery of this metabolic strategy potentially facilitates the design of novel therapeutic approaches to drug resistance.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Harper
authors.forename: Andreas
authors.initials: A
authors.lastname: Antoniou
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Villalobos-Menuey
authors.forename: Alicia
authors.initials: A
authors.lastname: Russo
authors.forename: Richard
authors.initials: R
authors.lastname: Trauger
authors.forename: Minda
authors.initials: M
authors.lastname: Vendemelio
authors.forename: Amanda
authors.initials: A
authors.lastname: George
authors.forename: Richard
authors.initials: R
authors.lastname: Bartholomew
authors.forename: Dennis
authors.initials: D
authors.lastname: Carlo
authors.forename: Azhar
authors.initials: A
authors.lastname: Shaikh
authors.forename: Jami
authors.initials: J
authors.lastname: Kupperman
authors.forename: Evan W
authors.initials: EW
authors.lastname: Newell
authors.forename: Ivan A
authors.initials: IA
authors.lastname: Bespalov
authors.forename: Susan S
authors.initials: SS
authors.lastname: Wallace
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Rogers
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Gibbs
authors.forename: Jack L
authors.initials: JL
authors.lastname: Leahy
authors.forename: Robert E
authors.initials: RE
authors.lastname: Camley
authors.forename: Robert
authors.initials: R
authors.lastname: Melamede
authors.forename: M Karen
authors.initials: MK
authors.lastname: Newell
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002945:Cisplatin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D003576:Electron Transport Complex IV / Q000378:metabolism; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008727:Methotrexate / Q000494:pharmacology; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000502:physiology; D019301:Oleic Acid / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
chemical_list: D019301:Oleic Acid; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D005947:Glucose; D002945:Cisplatin; D008727:Methotrexate