Induction of apoptosis by L-carnitine through regulation of two main pathways in Hepa1c1c 7 cells.
This study shows the effects of L-carnitine treatment on cell proliferation with hepa1c1c7 mouse cancer cells and NCTC 1469 normal cells. In an MTT assay, L-carnitine increased the number of dead hepa1c1c7 cells, while there was no difference in the number of NCTC 1469 cells. mRNA and protein levels of TNF-alpha, Fas, and caspase-8, which are closely related to cell apoptosis by a death ligand/receptor-dependent apoptosis pathway, were increased by L-carnitine treatment. In addition, L-carnitine treatment regulated mitochondria-dependent apoptosis pathways by inducing the up-regulation of caspase-9 and caspase-3 and the down-regulation of Bcl-2 in hepa1c1c 7 cells. Taken together, the findings of this study have demonstrated that L-carnitine could induce apoptosis in hepa1c1c7 cells by regulating Fas ligands and inhibiting the expression of Bcl-2. These results suggest that L: -carnitine treatment could be related to both a mitochondrion-dependent and a death ligand/receptor-dependent apoptosis pathway in hepa1c1c7 cells. Our results could give information for understanding the L-carnitine-induced apoptosis mechanism in some cancer cells.
Fan
Jiang Ping
JP
Department of Food Science and Technology, College of Natural Resources, Yeungnam University, Gyeongsan, Republic of Korea.
Kim
Han Seop
HS
Han
Gi Dong
GD
D000818:Animals; D017209:Apoptosis; D002331:Carnitine / Q000494:pharmacology*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053181:Caspase 8 / Q000187:drug effects / Q000378:metabolism; D053453:Caspase 9 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D053222:Fas Ligand Protein / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism; D019014:fas Receptor / Q000187:drug effects / Q000378:metabolism*
D053222:Fas Ligand Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D002331:Carnitine