JNK1-dependent antimitotic activity of thiazolidin compounds in human non-small-cell lung and colon cancer cells.
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.
Teraishi
F
F
Department of Thoracic and Cardiovascular Surgery, Unit 445, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Wu
S
S
Sasaki
J
J
Zhang
L
L
Davis
J J
JJ
Guo
W
W
Dong
F
F
Fang
B
B
D000814:Aniline Compounds / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D003110:Colonic Neoplasms / Q000201:enzymology*; D004789:Enzyme Activation; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology*; D008870:Microtubules / Q000187:drug effects; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D008941:Spindle Apparatus / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
C503119:5-((4-methylphenyl)methylene)-2-(phenylamino)-4(5H)-thiazolone; C503643:5-(2,4-dihydroxybenzylidene)-2-(phenylimino)-1,3-thiazolidin; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D013844:Thiazoles; D053778:Thiazolidines; D048055:Mitogen-Activated Protein Kinase 8