PMID- 21968419
OWN - NLM
STAT- MEDLINE
DCOM- 20120618
LR  - 20180815
IS  - 1473-5741 (Electronic)
IS  - 0959-4973 (Linking)
VI  - 23
IP  - 1
DP  - 2012 Jan
TI  - c-Jun N-terminal kinase mediates microtubule-depolymerizing agent-induced 
      microtubule depolymerization and G2/M arrest in MCF-7 breast cancer cells.
PG  - 98-107
LID - 10.1097/CAD.0b013e32834bc978 [doi]
AB  - Microtubule-binding agents (MBAs) form one of the most important anticancer-drug 
      families, but their molecular mechanisms are poorly understood. MBAs such as 
      paclitaxel (PTX) stabilize microtubules, whereas XRP44X (a novel pyrazole) and 
      combretastatins A4 (CA4) destabilize microtubules. These two different types of 
      MBAs have potent antitumor activity. Comparisons of their effects on signal 
      transduction and cellular responses will help uncover the molecular mechanism by 
      which MBAs affect tumor cells. We used MCF-7 cells to compare the effects of the 
      three MBAs on the cytoskeleton, cell cycle distribution, and activation of the 
      three major mitogen-activated protein kinase (MAPK) signaling cascades 
      [extracellular signal-related kinases, c-Jun N-terminal kinase (JNK), and p38 
      MAPK] using pharmacological inhibitors. The G2/M phase arrest was induced 
      following polymerization of microtubules by PTX and depolymerization by XRP44X 
      and CA4. The three major MAPKs were rapidly activated by XRP44X, and 
      extracellular signal-related kinases and p38 by PTX, whereas JNK did not quickly 
      respond to PTX. Pharmacological inhibitors indicated that activation of JNK is 
      principally required for XRP44X- and CA4-induced microtubule depolymerization and 
      G2/M phase arrest. Our results suggest that early phosphorylation of JNK is a 
      specific mechanism involved in microtubule depolymerization by certain MBAs.
FAU - Chen, Juan
AU  - Chen J
AD  - Laboratory of Tumor Molecular Diagnosis, West China Hospital, West China Medical 
      School, Sichuan University, Chengdu, People's Republic of China.
FAU - Sun, Wei-Liang
AU  - Sun WL
FAU - Wasylyk, Bohdan
AU  - Wasylyk B
FAU - Wang, Yan-Ping
AU  - Wang YP
FAU - Zheng, Hong
AU  - Zheng H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Anticancer Drugs
JT  - Anti-cancer drugs
JID - 9100823
RN  - 0 (Flavonoids)
RN  - 0 (Piperazines)
RN  - 0 (Pyrazoles)
RN  - 0 (Stilbenes)
RN  - 0 (XRP44X compound)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - I5590ES2QZ (fosbretabulin)
RN  - P88XT4IS4D (Paclitaxel)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Breast Neoplasms/*drug therapy/metabolism/*pathology
MH  - Cell Division/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Enzyme Activation/drug effects
MH  - Female
MH  - Flavonoids/pharmacology
MH  - G2 Phase/drug effects
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - MAP Kinase Signaling System
MH  - Microtubules/*drug effects
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Paclitaxel/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Piperazines/*pharmacology
MH  - Pyrazoles/*pharmacology
MH  - Stilbenes/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
EDAT- 2011/10/05 06:00
MHDA- 2012/06/19 06:00
CRDT- 2011/10/05 06:00
PHST- 2011/10/05 06:00 [entrez]
PHST- 2011/10/05 06:00 [pubmed]
PHST- 2012/06/19 06:00 [medline]
AID - 10.1097/CAD.0b013e32834bc978 [doi]
PST - ppublish
SO  - Anticancer Drugs. 2012 Jan;23(1):98-107. doi: 10.1097/CAD.0b013e32834bc978.