Increased mitochondrial palmitoylcarnitine/carnitine countertransport by flavone causes oxidative stress and apoptosis in colon cancer cells

Cell Mol Life Sci. 2005 Dec;62(24):3100-5. doi: 10.1007/s00018-005-5378-7.

Abstract

Cancer cell metabolism is characterized by limited oxidative phosphorylation in order to minimize oxidative stress. We have previously shown that the flavonoid flavone in HT-29 colon cancer cells increases the uptake of pyruvate or lactate into mitochondria, which is followed by an increase in O(2) (-.). production that finally leads to apoptosis. Similarly, a supply of palmitoylcarnitine in combination with carnitine induces apoptosis in HT-29 cells by increasing the mitochondrial respiration rate. Here we show that flavone-induced apoptosis is increased more than twofold in the presence of palmitoylcarnitine due to increased mitochondrial fatty acid transport and the subsequent metabolic generation of O(2) (-.) in mitochondria is the initiating factor for the execution of apoptosis.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Carnitine / metabolism*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Flavones / antagonists & inhibitors
  • Flavones / pharmacology*
  • HT29 Cells
  • Humans
  • Mitochondria / chemistry
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Palmitoylcarnitine / metabolism
  • Palmitoylcarnitine / pharmacology*
  • Superoxides / metabolism

Substances

  • Flavones
  • Superoxides
  • Palmitoylcarnitine
  • Carnitine