Sensitization of TRAIL-induced apoptosis in human hepatocellular carcinoma HepG2 cells by phytochemicals.

Abstract

AIMS:

The present study investigated and compared the potential chemosensitizing effect of indole-3-carbinol (I3C) and epigallocatechin-3-gallate (EGCG) on TRAIL-induced apoptosis in human hepatocellular carcinoma (HCC) HepG2 cells as well as the possible mechanisms underlying these modulatory effects, particularly their effects on TRAIL death receptors (DR), Bcl-2 and c-FLIP proteins expression.

MAIN METHODS:

HepG2 cells were treated with different concentrations of TRAIL ranging from 3 to 400ng/ml for 24h. For studying the modulatory effects of the phytochemicals on TRAIL-induced apoptosis, I3C and EGCG were used at concentrations that inhibit only 5% of the cells which were found to be 110μM and 70μg/ml, respectively.

KEY FINDINGS:

It was found that 24h pre-treatment of HepG2 cells with either 110μM I3C or 70μg/ml EGCG significantly enhanced TRAIL cytotoxicity. EGCG induced more reduction in IC50 of TRAIL compared to I3C. Nevertheless, I3C was more efficient than EGCG in enhancing TRAIL cytotoxicity at higher concentrations of TRAIL. Both I3C and EGCG significantly increased caspase-3 activity, DNA fragmentation percentage, DR4 and DR5 protein expression as well as decreased Bcl-2 protein expression when compared to control groups.

SIGNIFICANCE:

Both I3C and EGCG chemosensitized HCC HepG2 cells to TRAIL-induced apoptosis. These modulatory effects were partially attributed to the up-regulation of caspase-3 activity and DR4 and DR5 expression, as well as down-regulation of Bcl-2 expression. Only EGCG was able to induce a significant decrease in c-FLIP expression level.

• Authors: Reem N Abou El Naga, Samar S Azab, Ebtehal El-Demerdash, Sabry Shaarawy, Mahmoud El-Merzabani, el-Sayed M Ammar
• Journal: Life sciences (Life Sci) Vol. 92 Issue 10 Pg. 555-61 (Mar 21 2013) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 23352978 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• CASP8 and FADD-Like Apoptosis Regulating Protein
• CFLAR protein, human
• Indoles
• Proto-Oncogene Proteins c-bcl-2
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• TNF-Related Apoptosis-Inducing Ligand
• TNFSF10 protein, human
• Catechin
• epigallocatechin gallate
• indole-3-carbinol
• Caspase 3

Topics

• Apoptosis (drug effects)
• CASP8 and FADD-Like Apoptosis Regulating Protein (metabolism)
• Carcinoma, Hepatocellular (drug therapy)
• Caspase 3 (metabolism)
• Catechin (analogs & derivatives, pharmacology)
• DNA Fragmentation (drug effects)
• Dose-Response Relationship, Drug
• Hep G2 Cells
• Humans
• Indoles (pharmacology)
• Inhibitory Concentration 50
• Liver Neoplasms (drug therapy)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (metabolism)
• TNF-Related Apoptosis-Inducing Ligand (toxicity)