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

Cell Mol Life Sci. 2005 Oct;62(19-20):2382-9. doi: 10.1007/s00018-005-5365-z.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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


  • 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