skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Enhancement of esculetin on Taxol-induced apoptosis in human hepatoma HepG2 cells

Abstract

The potential use of low dose chemotherapy has been appealing since lower dosages are more attainable during cancer therapy and cause less toxicity in patients. Combination therapy of Taxol, a promising frontline chemotherapy agent, with natural anti-tumor agents that are considerably less toxic with a capability of activating additional apoptotic signals or inhibiting survival signals may provide a rational molecular basis for novel chemotherapeutic strategies. Esculetin, a well-known lipoxygenase inhibitor, showed an inhibitory effect on the cell cycle progression of HL-60 cells in our previous study. In this report, the effects of a concomitant administration of esculetin and Taxol were investigated in human hepatoma HepG2 cells. Firstly, esculetin alone could exert an antiproliferation effect together with an inhibitory effect on the activation of ERKs and p38 MAPK. As compared to the treatment with Taxol only, a co-administration with esculetin and Taxol could result in a further enhancement of apoptosis as revealed by DNA fragmentation assay and Annexin-V-based assay. Meanwhile, immunoblotting analysis also showed that the co-administration of esculetin and Taxol could increase the expression of Bax and the cytosolic release of cytochrome C and enhance the expression of Fas and Fas ligand while the activation of caspase-8 and caspase-3 wasmore » also increased. Finally, the ERK cascade was proven to be involved in the enhancement of esculetin on the Taxol-induced apoptosis.« less

Authors:
 [1];  [1];  [2];  [1];  [3]
  1. Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Chien Kuo N. Road, Taichung 402, Taiwan (China)
  2. School of Applied Chemistry, Chung Shan Medical University, No. 110, Section 1, Chien Kuo N. Road, Taichung 402, Taiwan (China)
  3. School of Applied Chemistry, Chung Shan Medical University, No. 110, Section 1, Chien Kuo N. Road, Taichung 402, Taiwan (China). E-mail: tht@csmu.edu.tw
Publication Date:
OSTI Identifier:
20783400
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 210; Journal Issue: 1-2; Other Information: DOI: 10.1016/j.taap.2005.06.020; PII: S0041-008X(05)00385-6; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL CYCLE; CHEMOTHERAPY; DMSO; DNA; HEPATOMAS; LIGANDS; PATIENTS; PROTEINS; TOXICITY

Citation Formats

Kuo, H.-C., Lee, H.-J., Hu, C.-C., Shun, H.-I, and Tseng, T.-H. Enhancement of esculetin on Taxol-induced apoptosis in human hepatoma HepG2 cells. United States: N. p., 2006. Web. doi:10.1016/j.taap.2005.06.020.
Kuo, H.-C., Lee, H.-J., Hu, C.-C., Shun, H.-I, & Tseng, T.-H. Enhancement of esculetin on Taxol-induced apoptosis in human hepatoma HepG2 cells. United States. doi:10.1016/j.taap.2005.06.020.
Kuo, H.-C., Lee, H.-J., Hu, C.-C., Shun, H.-I, and Tseng, T.-H. Sun . "Enhancement of esculetin on Taxol-induced apoptosis in human hepatoma HepG2 cells". United States. doi:10.1016/j.taap.2005.06.020.
@article{osti_20783400,
title = {Enhancement of esculetin on Taxol-induced apoptosis in human hepatoma HepG2 cells},
author = {Kuo, H.-C. and Lee, H.-J. and Hu, C.-C. and Shun, H.-I and Tseng, T.-H.},
abstractNote = {The potential use of low dose chemotherapy has been appealing since lower dosages are more attainable during cancer therapy and cause less toxicity in patients. Combination therapy of Taxol, a promising frontline chemotherapy agent, with natural anti-tumor agents that are considerably less toxic with a capability of activating additional apoptotic signals or inhibiting survival signals may provide a rational molecular basis for novel chemotherapeutic strategies. Esculetin, a well-known lipoxygenase inhibitor, showed an inhibitory effect on the cell cycle progression of HL-60 cells in our previous study. In this report, the effects of a concomitant administration of esculetin and Taxol were investigated in human hepatoma HepG2 cells. Firstly, esculetin alone could exert an antiproliferation effect together with an inhibitory effect on the activation of ERKs and p38 MAPK. As compared to the treatment with Taxol only, a co-administration with esculetin and Taxol could result in a further enhancement of apoptosis as revealed by DNA fragmentation assay and Annexin-V-based assay. Meanwhile, immunoblotting analysis also showed that the co-administration of esculetin and Taxol could increase the expression of Bax and the cytosolic release of cytochrome C and enhance the expression of Fas and Fas ligand while the activation of caspase-8 and caspase-3 was also increased. Finally, the ERK cascade was proven to be involved in the enhancement of esculetin on the Taxol-induced apoptosis.},
doi = {10.1016/j.taap.2005.06.020},
journal = {Toxicology and Applied Pharmacology},
number = 1-2,
volume = 210,
place = {United States},
year = {Sun Jan 15 00:00:00 EST 2006},
month = {Sun Jan 15 00:00:00 EST 2006}
}