alpha-Tocopheryl succinate-induced apoptosis in human gastric cancer cells is modulated by ERK1/2 and c-Jun N-terminal kinase in a biphasic manner.
Gastric neoplastic disease is one of the most frequent causes of cancer-associated deaths with poor prognosis. Here we studied the effect of the redox-silent analogue alpha-tocopheryl succinate (alpha-TOS), a strong apoptogen and anti-cancer agent, on the gastric cancer cell line SGC-7901. alpha-TOS inhibited proliferation of the cells and induced their apoptosis in a concentration- and time-dependent manner, while succinate or alpha-tocopherol showed no effect. The effect of alpha-TOS was modulated by components of the MAPK signaling network, including ERK1/2 and c-Jun N-terminal kinase (JNK), but not p38. Activation of ERK1/2 occurred early and increased until 12h, coinciding with an in crease in apoptosis in the cells, after which it dropped abruptly, while activation of JNK rose steadily, reaching a plateau at 12h of alpha-TOS treatment. The effects of ERK1/2 and JNK on the apoptosis outcome are transmitted via c-Jun, since transfection of the cells with c-Jun antisense oligodeoxynucleotide inhibited alpha-TOS-induced apoptosis. We conclude that ERK1/2 and JNK positively regulate apoptosis induced in gastric cancer cells by alpha-TOS.
Zhao
Yan
Y
Department of Nutrition and Food, Harbin Medical University, Harbin, Heilongjiang Province, China.
Zhao
Xiujuan
X
Yang
Baofeng
B
Neuzil
Jiri
J
Wu
Kun
K
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000473:pathology*; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D014810:Vitamin E; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D024505:Tocopherols