Increased mitochondrial palmitoylcarnitine/carnitine countertransport by flavone causes oxidative stress and apoptosis in colon cancer cells.
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.
Wenzel
U
U
Molecular Nutrition Unit, Department of Food and Nutrition, Technical University of Munich, Am Forum 5, 85350 Freising, Germany. uwenzel@wzw.tum.de
Nickel
A
A
Daniel
H
H
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002331:Carnitine / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D047309:Flavones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010172:Palmitoylcarnitine / Q000378:metabolism / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D047309:Flavones; D013481:Superoxides; D010172:Palmitoylcarnitine; D002331:Carnitine