Induction of apoptosis by linoleic acid is associated with the modulation of Bcl-2 family and Fas/FasL system and activation of caspases in AGS human gastric adenocarcinoma cells.
In this study, we investigated the effects of linoleic acid (LA), a polyunsaturated fatty acid found in most vegetable oils and certain food products, on the growth of AGS human gastric adenocarcinoma cells. LA treatment resulted in a concentration-dependent growth inhibition of AGS cells by inducing apoptosis, as evidenced by the formation of apoptotic bodies, chromatin condensation, and the accumulation cells in the sub-G1 phase. LA treatment induced cyclin-dependent kinase inhibitor p21 in a p53-independent manner; however, this compound did not affect the cell cycle distribution. Reverse transcription-polymerase chain reaction and western blot analyses showed that treating the cells with LA caused the up-regulation of pro-apoptotic Bax expression and the down-regulation of anti-apoptotic Bcl-2 expression. The apoptosis of AGS cells by LA was found to be associated with an elevated Fas and Fas ligand expression in a concentration-dependent manner. Furthermore, a proteolytic activation of caspases (3, 8, and 9), and degradation/cleavage of poly(ADP-ribose) polymerase and phospholipase C-gamma 1 protein were noted in LA-treated AGS cells. The present results indicate that the Fas/Fas ligand pathway might be involved in LA-induced apoptosis of AGS cells.
Kwon
Jae Im
JI
Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan, Republic of Korea.
Kim
Gi-Young
GY
Park
Kun Young
KY
Ryu
Chung Ho
CH
Choi
Yung Hyun
YH
D000230:Adenocarcinoma; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D053222:Fas Ligand Protein / Q000032:analysis / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms; D010738:Type C Phospholipases / Q000032:analysis; D019014:fas Receptor / Q000032:analysis / Q000235:genetics*
D053222:Fas Ligand Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D019014:fas Receptor; D019787:Linoleic Acid; D011065:Poly(ADP-ribose) Polymerases; D010738:Type C Phospholipases; D020169:Caspases