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, subG0/G1 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 (MMP), but these parameters were not significantly changed after PUFA pretreatment.
Hofmanová
Jiøina
J
Laboratory of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, CZ-612 65 Brno, Czech Republic. hofmanova@ibp.cz
Vaculová
Alena
A
Kozubík
Alois
A
D000230:Adenocarcinoma / Q000473:pathology*; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001095:Arachidonic Acids / Q000494:pharmacology*; D049109:Cell Proliferation; D024161:Collagen Type XI / Q000378:metabolism; D003110:Colonic Neoplasms / Q000473:pathology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation; D008928:Mitochondria; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000906:Antibodies; D001095:Arachidonic Acids; C481004:CH-11 anti-fas antibody, human; C499319:COL11A2 protein, human; D024161:Collagen Type XI; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases