JNK1-dependent antimitotic activity of thiazolidin compounds in human non-small-cell lung and colon cancer cells
| Autor: | Bingliang Fang, Fuminori Teraishi, John J. Davis, Fengqing Dong, Ji-Ichiro Sasaki, Lidong Zhang, Shuhong Wu, Wei Guo |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Lung Neoplasms
Mitosis Antineoplastic Agents Cell Cycle Proteins Spindle Apparatus Biology Microtubules Article Cellular and Molecular Neuroscience Enzyme activator Histone H3 Carcinoma Non-Small-Cell Lung Humans Mitogen-Activated Protein Kinase 8 Cyclin B1 Molecular Biology Pharmacology Aniline Compounds Cell Biology Cell cycle Cell biology Enzyme Activation Thiazoles Cancer cell Colonic Neoplasms Cancer research Molecular Medicine Phosphorylation Thiazolidines Multipolar spindles |
| Zdroj: | Cellular and molecular life sciences : CMLS. 62(19-20) |
| ISSN: | 1420-682X |
| Popis: | We recently identified two thiazolidin compounds, 5-[(4-methylphenyl)methylene]-2-(phenylamino)-4(5H)-thiazolone (MMPT) and 5-(2,4-dihydroxybenzylidene)-2-(phenylimino)-1,3-thiazolidin (DBPT), that inhibit the growth of human non-small-cell lung and colon cancer cells independent of P-glycoprotein and p53 status. Here we further investigated the mechanism by which these thiazolidin compounds mediate their anticancer effects. Treatment of cancer cells with MMPT and DBPT led to a time-dependent accumulation of cells arrested in the G2/M phase with modulation of the expression of proteins such as cyclin B1, cdc25C, and phosphorylated histone H3. Moreover, treatment with MMPT and DBPT increased M-phase arrest with abnormal spindle formation. DBPT-mediated G2/M phase arrest and phosphorylation of cdc25C and histone H3 were abrogated when JNK activation was blocked either with SP600125, a specific JNK inhibitor, or a dominant-negative JNK1 gene. Moreover, DBPT-mediated microtubule disruption was also blocked by SP600125 treatment. Our results demonstrate that thiazolidin compounds can effectively induce G2/M arrest in cancer cells and that this G2/M arrest requires JNK activation. |
| Databáze: | OpenAIRE |
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