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

Oral Oncol. 2009 Dec;45(12):1067-72. doi: 10.1016/j.oraloncology.2009.07.018. Epub 2009 Aug 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

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