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 language | English |
|---|---|
| Pages (from-to) | 2382-2389 |
| Number of pages | 8 |
| Journal | Cellular and Molecular Life Sciences |
| Volume | 62 |
| Issue number | 19-20 |
| DOIs | |
| Publication status | Published - Oct 2005 |
| Externally published | Yes |
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
