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Research ArticleExperimental Studies

Coumarin Induces Cell Cycle Arrest and Apoptosis in Human Cervical Cancer HeLa Cells through a Mitochondria- and Caspase-3 Dependent Mechanism and NF-κB Down-regulation

JING-YUAN CHUANG, YUNG-FENG HUANG, HSU-FENG LU, HENG-CHEN HO, JAI-SING YANG, TE-MAO LI, NAI-WEN CHANG and JING-GUNG CHUNG
In Vivo November 2007, 21 (6) 1003-1009;
JING-YUAN CHUANG
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YUNG-FENG HUANG
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HSU-FENG LU
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HENG-CHEN HO
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JAI-SING YANG
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TE-MAO LI
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NAI-WEN CHANG
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JING-GUNG CHUNG
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  • For correspondence: jgchung@mail.cmu.edu.tw
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Abstract

The effects of coumarin on cell viability, cell cycle arrest and induction of apoptosis were investigated in human cervical cancer HeLa cells. Coumarin was cytotoxic with an IC50 of 54.2 μM, induced morphological changes, and caused G0/G1 arrest and apoptosis. The decreasing number of viable cells appeared to be due to induction of cell cycle arrest and apoptotic cell death, since coumarin induced morphologically apoptotic changes and internucleosomal DNA laddering fragmentation and increased the sub-G1 group. Coumarin affected the production of reactive oxygen species and Ca2+ concentration, and dose-dependently induced the depolarization of mitochondrial membrane potential. Also, coumarin treatment gradually decreased the expression of G0/G1-associated proteins which may have led to the G0/G1 arrest, and the anti-apoptotic proteins Bcl-2 and Bcl-xL, and increased the expression of the pro-apoptotic protein Bax. Coumarin decreased the mitochondrial membrane potential and promoted the release of cytochrome c and the activation of caspase-3 before leading to apoptosis. These results provide information on the mechanisms by which coumarin induces cell cycle arrest and apoptosis in human cervical cancer cells (HeLa).

  • Coumarin
  • apoptosis
  • cell cycle
  • caspase-3
  • NF-κB
  • mitochondria

Footnotes

  • Received June 11, 2007.
  • Revision received September 5, 2007.
  • Accepted October 2, 2007.
  • Copyright © 2007 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Vol. 21, Issue 6
November-December 2007
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Coumarin Induces Cell Cycle Arrest and Apoptosis in Human Cervical Cancer HeLa Cells through a Mitochondria- and Caspase-3 Dependent Mechanism and NF-κB Down-regulation
JING-YUAN CHUANG, YUNG-FENG HUANG, HSU-FENG LU, HENG-CHEN HO, JAI-SING YANG, TE-MAO LI, NAI-WEN CHANG, JING-GUNG CHUNG
In Vivo Nov 2007, 21 (6) 1003-1009;

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Coumarin Induces Cell Cycle Arrest and Apoptosis in Human Cervical Cancer HeLa Cells through a Mitochondria- and Caspase-3 Dependent Mechanism and NF-κB Down-regulation
JING-YUAN CHUANG, YUNG-FENG HUANG, HSU-FENG LU, HENG-CHEN HO, JAI-SING YANG, TE-MAO LI, NAI-WEN CHANG, JING-GUNG CHUNG
In Vivo Nov 2007, 21 (6) 1003-1009;
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