Synergistic action of piroxicam on the eicosapentaenoic acid-induced apoptosis is associated with enhanced down-regulation of anti-apoptotic Bcl-2 expression but not promoted activation of pro-apoptotic Bid protein.
Eicosapentaenoic acid (EPA) is a dietary polyunsaturated fatty acid (PUFA) that is found abundantly in fish oils and induces apoptosis in human promyelocytic leukemia HL-60 cells. Cyclooxygenase (COX) converts EPA intracellularly into various inflammatory mediators that may affect the bioavailability of this fatty acid for inducing apoptosis in the cancer cells. In this study, effect of piroxicam (PRX), a COX inhibitor, on the EPA-induced apoptosis in HL-60 cells was investigated. EPA arrested cell cycle of the leukemic cells at G0/G1 phase after 8-h incubation and induced apoptosis after 24-h incubation. PRX induced neither cell-cycle arrest nor apoptosis significantly in HL-60 cells even after 48-h incubation. However, 24-h incubation with PRX followed by 24-h incubation with EPA significantly elevated both early-phase and late-phase apoptotic cells by 35% and 166% respectively, when compared to those induced by the fatty acid only. This synergistic action of PRX on the EPA-induced apoptosis was associated with enhanced down-regulation of anti-apoptotic Bcl-2 protein expression, but not promoted activation of pro-apoptotic Bid protein.
Chiu
Lawrence C-M
LC
Department of Biology, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China. chimingchiu@cuhk.edu.hk
Tong
K-F
KF
Ooi
Vincent E C
VE
D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation; D004357:Drug Synergism; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D010894:Piroxicam / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors
D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D002352:Carrier Proteins; D016861:Cyclooxygenase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D010894:Piroxicam; D015118:Eicosapentaenoic Acid