Ampelopsin Induces DR5-Mediated Apoptotic Cell Death in EBV-Infected Cells through the p38 Pathway

Abstract

Ampelopsin (AMP) is a well-known flavonoid that exerts a number of biological and pharmacological effects including anticancer effects against several cancer cell lines. In this study, we investigated the anticancer activity of AMP against Epstein-Barr virus (EBV)-positive cells and its mechanism of action. Our results showed that AMP dose-dependently inhibited cell viability and induced apoptotic cell death in EBV-positive cells without cytotoxicity in EBV-negative cells. In particular, AMP induced caspase-8 dependent apoptosis via upregulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and death receptor (DR5). Knockdown of DR5 by RNA interference blocked AMP-induced apoptosis. Furthermore, AMP dose-dependently activated p38 mitogen-activated protein kinases (MAPKs) in EBV-positive cells. Additionally, SB203580 (a p38-MAPK inhibitor) effectively inhibited apoptotic cell death. These results demonstrate that treatment with AMP induces the apoptosis of EBV-positive cells through upregulation of TRAIL/DR5 and activation of p38 signaling. Therefore, these results provide experimental information for developing AMP as a new therapeutic drug against EBV-positive cancer.

Disclosure Statement

All authors have no conflicts of interest about this work.

Funding

This work was supported by the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare Affairs, Republic of Korea under Grant number HI15C2800.

Author Contributions

Ki Hoon Kim and Dae Young Hur contributed to conception and design and interpretation of data; Sun-Mi Yun and Yeong Seok Kim contributed to acquisition of data, analysis of data, and interpretation of data; Sun-mi Yuna and Dae Young Hur contributed to drafting the article and revising it critically for important intellectual content; Dae Young Hur contributed to final approval of the version to be published.