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

F. Teraishi, S. Wu, J. Sasaki, L. Zhang, J. J. Davis, W. Guo, F. Dong, B. Fang

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2382-2389
Number of pages8
JournalCellular and Molecular Life Sciences
Volume62
Issue number19-20
DOIs
Publication statusPublished - Oct 2005

Keywords

  • Cancer therapy
  • Cell cycle
  • Microtubule disruption
  • Mitotic arrest
  • Non-small-cell lung cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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