JNK1-dependent antimitotic activity of thiazolidin compounds in human non-small-cell lung and colon cancer cells.

Abstract

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.

• Authors: F Teraishi, S Wu, J Sasaki, L Zhang, J J Davis, W Guo, F Dong, B Fang
• Journal: Cellular and molecular life sciences : CMLS (Cell Mol Life Sci) Vol. 62 Issue 19-20 Pg. 2382-9 (Oct 2005) ISSN: 1420-682X [Print] Switzerland
• PMID: 16179969 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 5-((4-methylphenyl)methylene)-2-(phenylamino)-4(5H)-thiazolone
• 5-(2,4-dihydroxybenzylidene)-2-(phenylimino)-1,3-thiazolidin
• Aniline Compounds
• Antineoplastic Agents
• Cell Cycle Proteins
• Thiazoles
• Thiazolidines
• Mitogen-Activated Protein Kinase 8

Topics

• Aniline Compounds (pharmacology)
• Antineoplastic Agents (pharmacology)
• Carcinoma, Non-Small-Cell Lung (enzymology)
• Cell Cycle Proteins (metabolism)
• Colonic Neoplasms (enzymology)
• Enzyme Activation
• Humans
• Lung Neoplasms (enzymology)
• Microtubules (drug effects)
• Mitogen-Activated Protein Kinase 8 (metabolism)
• Mitosis (drug effects)
• Spindle Apparatus (drug effects)
• Thiazoles (pharmacology)
• Thiazolidines