Polyunsaturated fatty acids sensitize human colon adenocarcinoma HT-29 cells to death receptor-mediated apoptosis
The proliferative and apoptotic response to TNF-alpha and anti-Fas antibody (CH- 11) in human colon adenocarcinoma HT-29 cells was modulated by pretreatment with arachidonic (AA, 20:4, n - 6) or docosahexaenoic (DHA, 22:6, n - 3) fatty acids, which alone increased reactive oxygen species production and lipid peroxidation, and decreased the S-phase of the cell cycle. The higher amount of floating cells, subG(0)/G(1) population and apoptotic cells detected in pre-treated cells was potentiated by cycloheximide. The effects of CH-11 were associated with activation of caspase-8, -9, and -3, cleavage of poly(ADP-ribose)polymerase-PARP, and decreased mitochondrial membrane potential (NIMP), but these parameters were not significantly changed after PUFA pretreatment. (C) 2004 Elsevier Ireland Ltd. All rights reserved.