QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wenzel, U. Articles by Daniel, H. Search for Related Content PubMed PubMed Citation Articles by Wenzel, U. Articles by Daniel, H.

---

Nutrition and Cancer

Increased Carnitine-Dependent Fatty Acid Uptake into Mitochondria of Human Colon Cancer Cells Induces Apoptosis

Molecular Nutrition Unit, Department of Food and Nutrition, Technical University of Munich, Hochfeldweg 2, D-85350 Freising, Germany

¹To whom correspondence should be addressed. E-mail: uwenzel{at}wzw.tum.de.

Carnitine-dependent fatty acid import into mitochondria and ß-oxidation seem to be impaired in tumor cells. In the present study we show that a supply of palmitoylcarnitine together with L-carnitine potently induces apoptosis in HT-29 human colon cancer cells as a consequence of accelerated fatty acid oxidation. Caspase-3-like activities, measured by the cleavage rate of a fluorogenic tetrapeptide substrate and nuclear fragmentation determined after DNA labeling in fixed cells by fluorescence microscopy, served as indicators of apoptosis. Neither L-carnitine nor palmitoylcarnitine alone were able to increase caspase-3-like activities and DNA fragmentation, but when provided together, apoptosis occurred. That exogenous carnitine was indeed able to enhance fatty acid uptake into mitochondria was demonstrated by an increased influx of a fluorescent palmitic acid analog. Enhanced fatty acid availability in mitochondria led to an increased generation of O₂^–·, as detected by a O₂^–·-sensitive fluorogenic dye, indicating oxidation of delivered substrates. Benzoquinone, an O₂^–· scavenger, blocked O₂^–· generation and prevented apoptosis as initiated by the combination of palmitoylcarnitine and carnitine. The lack of effect of the ceramide synthesis inhibitor fumonisin on palmitoylcarnitine/carnitine-induced apoptosis further supports the notion that apoptotic cell death is specifically due to fatty acid oxidation. In contrast to HT-29 cells, nontransformed human colonocytes did not respond to exogenous palmitoylcarnitine/carnitine and no apoptosis was observed. In conclusion, our studies provide evidence that a limited mitochondrial fatty acid import in human colon cancer cells prevents high rates of mitochondrial O₂^–· production and protects colon cancer cells from apoptosis that can be overcome by an exogenous carnitine supply.

KEY WORDS: • HT-29 human colon cancer cells • carnitine • apoptosis • mitochondrial substrate oxidation • superoxide anions

This article has been cited by other articles:

				I. Winkelmann, D. Diehl, D. Oesterle, H. Daniel, and U. Wenzel The suppression of aberrant crypt multiplicity in colonic tissue of 1,2-dimethylhydrazine-treated C57BL/6J mice by dietary flavone is associated with an increased expression of Krebs cycle enzymes Carcinogenesis, July 1, 2007; 28(7): 1446 - 1454. [Abstract] [Full Text] [PDF]

				M. E. Juan, U. Wenzel, V. Ruiz-Gutierrez, H. Daniel, and J. M. Planas Olive Fruit Extracts Inhibit Proliferation and Induce Apoptosis in HT-29 Human Colon Cancer Cells J. Nutr., October 1, 2006; 136(10): 2553 - 2557. [Abstract] [Full Text] [PDF]