Induction of endoreduplication by a JNK inhibitor SP600125 in human lung carcinoma A 549 cells.
The effect of the pan c-Jun N-terminal kinase (JNK) inhibitor SP600125 on the proliferation of human lung carcinoma A549 cells has been evaluated. We have shown that SP600125 completely inhibited the proliferation of A549 cells, the cycle arrest being in G2/M phase. When cells were treated with SP600125 for >12h, a cell population with DNA content of 4n to 8n was detected. Moreover, the effect of SP600125 on the expression of cell cycle related proteins was an upregulation of p53 protein accompanied by an increase in its molecular mass. Prolonged SP600125 treatment downregulated p21, Bax and Mdm2 expression, but increased the level of the cellular p53-Mdm2 complex. Taken together, we show that SP600125 could induce G2/M cell cycle arrest and endoreduplication in a p21 independent manner, and that SP600125 could also post-translationally modify p53 to modify its function. Our data show that basic JNK activity plays an important role in the progression of the cell cycle at G2/M cell phase.
Miyamoto-Yamasaki
Yumi
Y
Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Fukuoka 812-8581, Japan. yumi_mi_1111@yahoo.co.jp
Yamasaki
Masao
M
Tachibana
Hirofumi
H
Yamada
Koji
K
D000873:Anthracenes / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000502:physiology*; D016195:G2 Phase / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011123:Polyploidy; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D019253:Proto-Oncogene Proteins c-bcl-2; D051736:Proto-Oncogene Proteins c-mdm2; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53
D000873:Anthracenes; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C432165:pyrazolanthrone; D004247:DNA; D051736:Proto-Oncogene Proteins c-mdm2; D048031:JNK Mitogen-Activated Protein Kinases