Fatty acid oxidation and carnitine palmitoyltransferase I: emerging therapeutic targets in cancer

Cell Death Dis. 2016 May 19;7(5):e2226. doi: 10.1038/cddis.2016.132.

Abstract

Tumor cells exhibit unique metabolic adaptations that are increasingly viewed as potential targets for novel and specific cancer therapies. Among these targets, the carnitine palmitoyltransferase system is responsible for delivering the long-chain fatty acid (FA) from cytoplasm into mitochondria for oxidation, where carnitine palmitoyltransferase I (CPTI) catalyzes the rate-limiting step of fatty acid oxidation (FAO). With increasing understanding of the crucial role had by fatty acid oxidation in cancer, CPTI has received renewed attention as a pivotal mediator in cancer metabolic mechanism. CPTI activates FAO and fuels cancer growth via ATP and NADPH production, constituting an essential part of cancer metabolism adaptation. Moreover, CPTI also functionally intertwines with other key pathways and factors to regulate gene expression and apoptosis of cancer cell. Here, we summarize recent findings and update the current understanding of FAO and CPTI in cancer and provide theoretical basis for this enzyme as an emerging potential molecular target in cancer therapeutic intervention.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / antagonists & inhibitors
  • Adenosine Triphosphate / biosynthesis
  • Antineoplastic Agents / pharmacology*
  • Carnitine / analogs & derivatives*
  • Carnitine / pharmacology
  • Carnitine O-Palmitoyltransferase / antagonists & inhibitors*
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / metabolism
  • Cytoplasm / drug effects
  • Cytoplasm / enzymology
  • Cytoplasm / pathology
  • Fatty Acids / antagonists & inhibitors
  • Fatty Acids / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics
  • Mitochondria / drug effects
  • Mitochondria / enzymology
  • Mitochondria / pathology
  • Molecular Targeted Therapy
  • NADP / antagonists & inhibitors
  • NADP / biosynthesis
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Oxidation-Reduction

Substances

  • Antineoplastic Agents
  • Fatty Acids
  • Isoenzymes
  • ST1326
  • NADP
  • Adenosine Triphosphate
  • Carnitine O-Palmitoyltransferase
  • carnitine palmitoyltransferase 1A, human
  • Carnitine