Induction of apoptosis and cell cycle arrest by a specific c-Jun NH2-terminal kinase (JNK) inhibitor, SP-600125, in gastrointestinal cancers.
The c-Jun NH(2)-terminal kinase (JNK) is activated in several tumor cell lines. The aim of this study was to determine the effects of SP-600125, a specific JNK inhibitor, on the viability, apoptosis, cell cycle distribution of gastrointestinal cancer cells, and the potential anti-tumor mechanisms. Three gastric cancer cell lines, AGS, BCG-823 and MKN-45, and three colorectal cancer cell lines, SW1116, COLO205 and HT-29, were used. Cells were treated with SP-600125, and cell viability, apoptosis and cell cycle distribution, caspase-3 activity, expression of JNK and apoptosis related proteins were detected. SP-600125 inhibited cell proliferation by 10-80% for the different cell lines, and increased apoptosis by 1.5-4.5 folds for COLO205, BCG-823, MKN-45, AGS cells. Caspase-8 and caspase-3 were involved in the induction of apoptosis. SP-600125 caused G2/M cell cycle arrest and elevation of cyclin B1 and p27(kip). The differential response in cells to SP-600125 was associated with the basal level of phosphorylated JNK2. It is concluded that SP-600125 inhibits proliferation, induces apoptosis and causes cell cycle arrest in gastrointestinal cancer cells, indicating that JNK inhibitors have an anti-tumor effect and are potential therapeutic agents for cancers.
Xia
Harry Hua-Xiang
HH
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China.
He
Hua
H
De Wang
Ji
J
Gu
Qing
Q
Lin
Marie C M
MC
Zou
Bing
B
Yu
Li Fen
LF
Sun
Yun Wei
YW
Chan
Annie O O
AO
Kung
Hsiang Fu
HF
Wong
Benjamin Chun-Yu
BC
D000873:Anthracenes / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000873:Anthracenes; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases