Apoptosis induction by p38 MAPK inhibitor in human colon cancer cells.
OBJECTIVE
The p38 mitogen-activated protein kinases (p38 MAPKs) function in a wide variety of signaling pathways. However, the role of p38s is cell type- and stimulus-dependent. The present study aimed to evaluate the effects of p38 MAPK inhibitor on human colon cancer cells.


METHODS
The effect of p38 MAPK inhibitor, FR167653, on DLD-1 and SW480 was investigated related to cell proliferation, apoptosis induction and caspase activity. Additionally, the effect of FR167653 on colon cancer cell migration, MMPs production and ability to adhere to extracellular matrix was investigated.


RESULTS
Inhibitor of p38 MAPK dose-dependently suppressed the proliferative activity of both cell lines, and increased the induction of cell apoptosis. The caspase-3, 8, and 9 activities were accompanied in the pathway. Neither cell migration, MMPs production, nor the ability to adhere extracellular matrix were affected by FR167653.


CONCLUSIONS
Inhibitor of p38 MAPK suppressed the proliferation of colon cancer cells by induction of cell apoptosis through the caspase activation. The present results suggest the pro-oncogenic role ofp38 in colon cancer, and its inhibition would be a novel strategy for the prevention and treatment of colon cancer.
Tsuchiya
Takeshi
T
Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Tokyo, Japan. tk-tsuchiya@muh.biglobe.ne.jp
Tsuno
Nelson H
NH
Asakage
Masahiro
M
Yamada
Jun
J
Yoneyama
Satomi
S
Okaji
Yurai
Y
Sasaki
Shin
S
Kitayama
Joji
J
Osada
Takuya
T
Takahashi
Koki
K
Nagawa
Hirokazu
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D006801:Humans; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; C104334:FR 167653; D011720:Pyrazoles; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases