TY - JOUR
T1 - JNK1-dependent antimitotic activity of thiazolidin compounds in human non-small-cell lung and colon cancer cells
AU - Teraishi, F.
AU - Wu, S.
AU - Sasaki, J.
AU - Zhang, L.
AU - Davis, J. J.
AU - Guo, W.
AU - Dong, F.
AU - Fang, B.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/10
Y1 - 2005/10
N2 - 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.
AB - 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.
KW - Cancer therapy
KW - Cell cycle
KW - Microtubule disruption
KW - Mitotic arrest
KW - Non-small-cell lung cancer
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U2 - 10.1007/s00018-005-5365-z
DO - 10.1007/s00018-005-5365-z
M3 - Article
C2 - 16179969
AN - SCOPUS:27144450237
VL - 62
SP - 2382
EP - 2389
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
SN - 1420-682X
IS - 19-20
ER -