Induction of apoptosis by polyunsaturated fatty acids and its relationship to fatty acid inhibition of carnitine palmitoyltransferase I activity in Hep2 cells

Abstract

The effects of fatty acids on the induction of apoptosis were studied over a 24 hour period in Hep2 human larynx tumour cells. While oleic and linoleic acids had little effect on the apoptotic index, the polyunsaturated fatty acids α-linolenic, γ-linolenic, arachidonic, eicosapentaenoic and docosahexaenoic acids all induced apoptosis, beginning at ~ 6 hours after fatty acid exposure. By 24 hours after exposure, the apoptotic index had reached as much as 19% in the presence of docosahexaenoic or α-linolenic acid. The correlation between degree of unsaturation of the 18-carbon fatty acids and the apoptotic index was r2 = 0.45, 0.89, 0.84 and 0.98 at 6, 8, 12 and 24 hours, respectively. The correlation between mitochondrial carnitine palmitoyltransferase I (CPT I) activity, 6 hours after exposure, and the apoptotic index was r2 = 0.842 and 0.798 at 12 and 24 hours, respectively. The inhibition of CPT I and subsequent fatty acid oxidation by polyunsaturated fatty acids leads to a significant increase in apoptosis, suggesting that CPT I may be involved in the processes of programmed cell death in Hep2 human tumour cells.