Activation of caspase 3 in HepG2 cells by elaidic acid (t18:1)

In order to examine the effects of trans-unsaturated fatty acids (TFAs) on HepG2 cells, cells were grown in serum-free media supplemented with elaidic acid (t18:1); t18:1 is the trans-isomer of oleic acid and is the major component of TFAs in foods. Both t18:1 and palmitic acids (16:0) at concentrations higher than 100 mu M inhibited growth and decreased the rate of protein synthesis. The presence of phosphatidylserine in the outer leaflet of the lipid bilayer, indicative of apoptosis, occurred 1 h after the addition of both t18:1 and 16:0 to the media. Caspase 3 was found to be activated by these fatty acids: caspase 8 was activated by 16:0 and only moderately by it 8:1. Activation of caspase 3 by these fatty acids was fully inhibited by a caspase 8 inhibitor. However, growth inhibition by t18:1 was partially prevented by the caspase 8 inhibitor. These results suggest that cell death caused by t18:1 may proceed by both caspase-dependent and -independent pathways. (C) 2007 Elsevier B.V. All rights reserved.