Esculetin enhances TRAIL-induced apoptosis through DR5 upregulation in human oral cancer SAS cells.

Abstract

Esculetin has been shown to selectively induce tumor apoptosis in several types of cancers and is regarded as a promising chemotherapeutic agent. In this study, we showed that esculetin significantly suppressed the growth of oral cancer SAS cells in a dose-dependent manner. DNA content flow cytometry and TUNEL assay revealed that esculetin induced cell cycle arrest and apoptosis. Western blotting showed esculetin increased DR5 protein expression and activated caspase-8, which differed from previous studies conducted in other cell types. Furthermore, treatment with esculetin significantly increased TRAIL-induced apoptosis in SAS cells and the TRAIL-sensitizing effect was blocked by DR5/Fc chimera protein. Our results indicate that esculetin enhances TRAIL-induced apoptosis primarily through upregulation of DR5. Combination of esculetin and TRAIL may be a novel treatment strategy for oral cancers.

• Authors: Sang-Heng Kok, Cheng-Chang Yeh, Mei-Ling Chen, Mark Yen-Ping Kuo
• Journal: Oral oncology (Oral Oncol) Vol. 45 Issue 12 Pg. 1067-72 (Dec 2009) ISSN: 1879-0593 [Electronic] England
• PMID: 19720557 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Neoplasm Proteins
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• Umbelliferones
• Caspase 8
• esculetin

Topics

• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Caspase 8 (metabolism)
• Cell Cycle (drug effects)
• Flow Cytometry
• Humans
• In Situ Nick-End Labeling
• Mouth Neoplasms (metabolism)
• Neoplasm Proteins (metabolism)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (metabolism)
• Umbelliferones (pharmacology)