Cell type-dependent effects of ellagic acid on cellular metabolism

Biomed Pharmacother. 2018 Oct:106:411-418. doi: 10.1016/j.biopha.2018.06.142. Epub 2018 Jul 11.

Abstract

Ellagic acid is a botanical polyphenol which has been shown to have numerous effects on cellular function. Ellagic acid can induce apoptosis and inhibit the proliferation of various cancer cell types in vitro and in vivo. As such, ellagic acid has attracted significant interest as a potential chemotherapeutic compound. One mechanism by which ellagic acid has been proposed to affect cellular physiology is by regulating metabolic pathways. Here we show the dose-dependent effects of ellagic acid on cellular energy production and downstream induction of the apoptotic program in HEK293, HeLa, MCF7, and HepG2 cells. At physiologically relevant doses, ellagic acid has pleiotropic and cell-type specific effects on mitochondrial function. At high doses ellagic acid can also influence glycolytic pathways and induce cell death. Our results demonstrate that ellagic acid can influence mitochondrial function at therapeutically relevant concentrations. The observed effects of ellagic acid on cellular respiration are complex and cell type-specific, which may limit the chemotherapeutic utility of this compound.

Keywords: Apoptosis; Cancer; Ellagic acid; Glycolysis; Mitochondria; Respiration.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Caspase 6 / metabolism
  • Dose-Response Relationship, Drug
  • Ellagic Acid / pharmacology*
  • Energy Metabolism / drug effects*
  • HEK293 Cells
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Time Factors

Substances

  • Antineoplastic Agents, Phytogenic
  • Ellagic Acid
  • Adenosine Triphosphate
  • CASP3 protein, human
  • CASP6 protein, human
  • Caspase 3
  • Caspase 6