Esculetin enhances TRAIL-induced apoptosis through DR5 upregulation in human oral cancer SAS cells.
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.
Kok
Sang-Heng
SH
School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yeh
Cheng-Chang
CC
Chen
Mei-Ling
ML
Kuo
Mark Yen-Ping
MY
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053181:Caspase 8 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D009062:Mouth Neoplasms / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D014468:Umbelliferones / Q000494:pharmacology*
D000975:Antioxidants; D009363:Neoplasm Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D014468:Umbelliferones; D053181:Caspase 8; C007628:esculetin