PMID- 22266726
OWN - NLM
STAT- MEDLINE
DCOM- 20120815
LR  - 20211021
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 33
IP  - 3
DP  - 2012 Mar
TI  - Novel microtubule-targeted agent 6-chloro-4-(methoxyphenyl) coumarin induces G2-M 
      arrest and apoptosis in HeLa cells.
PG  - 407-17
LID - 10.1038/aps.2011.176 [doi]
AB  - AIM: To identify a novel coumarin analogue with the highest anticancer activity 
      and to further investigate its anticancer mechanisms. METHODS: The viability of 
      cancer cells was investigated using the MTT assay. The cell cycle progression was 
      evaluated using both flow cytometric and Western blotting analysis. Microtubule 
      depolymerization was observed with immunocytochemistry in vivo and a tubulin 
      depolymerization assay in vitro. Apoptosis was demonstrated using Annexin 
      V/Propidium Iodide (PI) double-staining and sub-G(1) analysis. RESULTS: Among 36 
      analogues of coumarin, 6-chloro-4-(methoxyphenyl) coumarin showed the best 
      anticancer activity (IC(50) value about 200 nmol/L) in HCT116 cells. The compound 
      had a broad spectrum of anticancer activity against 9 cancer cell lines derived 
      from colon cancer, breast cancer, liver cancer, cervical cancer, leukemia, 
      epidermoid cancer with IC(50) value of 75 nmol/L-1.57 mumol/L but with low 
      cytotocitity against WI-38 human lung fibroblasts (IC(50) value of 12.128 
      mumol/L). The compound (0.04-10 mumol/L) induced G(2)-M phase arrest in HeLa cells 
      in a dose-dependent manner, which was reversible after the compound was removed. 
      The compound (10-300 mumol/L) induced the depolymerization of purified porcine 
      tubulin in vitro. Finally, the compound (0.04-2.5 mumol/L) induced apoptosis of 
      HeLa cells in dose- and time-dependent manners. CONCLUSION: 
      6-Chloro-4-(methoxyphenyl) coumarin is a novel microtubule-targeting agent that 
      induces G(2)-M arrest and apoptosis in HeLa cells.
FAU - Ma, Yi-ming
AU  - Ma YM
AD  - National Center for Drug Screening, State Key Laboratory of Drug Research, 
      Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
FAU - Zhou, Yu-bo
AU  - Zhou YB
FAU - Xie, Chuan-ming
AU  - Xie CM
FAU - Chen, Dong-mei
AU  - Chen DM
FAU - Li, Jia
AU  - Li J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120123
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Coumarins)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Cell Line, Tumor
MH  - Coumarins/*pharmacology
MH  - G2 Phase Cell Cycle Checkpoints/*drug effects
MH  - HeLa Cells
MH  - Humans
MH  - M Phase Cell Cycle Checkpoints/*drug effects
MH  - Microtubules/*drug effects
PMC - PMC4077132
EDAT- 2012/01/24 06:00
MHDA- 2012/08/16 06:00
PMCR- 2012/03/01
CRDT- 2012/01/24 06:00
PHST- 2012/01/24 06:00 [entrez]
PHST- 2012/01/24 06:00 [pubmed]
PHST- 2012/08/16 06:00 [medline]
PHST- 2012/03/01 00:00 [pmc-release]
AID - aps2011176 [pii]
AID - 10.1038/aps.2011.176 [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2012 Mar;33(3):407-17. doi: 10.1038/aps.2011.176. Epub 2012 
      Jan 23.