Oncotarget

Research Papers:

Activation of autophagic flux by epigallocatechin gallate mitigates TRAIL-induced tumor cell apoptosis via down-regulation of death receptors

Sung-Wook Kim, Ji-Hong Moon and Sang-Youel Park _

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Oncotarget. 2016; 7:65660-65668. https://doi.org/10.18632/oncotarget.11597

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Abstract

Sung-Wook Kim1,*, Ji-Hong Moon1,*, Sang-Youel Park1

1Biosafety Research Institute, Department of Veterinary Medicine, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk 54596, Republic of Korea

*These authors contributed equally to this work

Correspondence to:

Sang-Youel Park, email: sypark@chonbuk.ac.kr

Keywords: EGCG, autophagy, TRAIL, death receptor

Received: February 13, 2016     Accepted: August 13, 2016     Published: August 25, 2016

ABSTRACT

Epigallocatechin gallate (EGCG) is a major polyphenol in green tea. Recent studies have reported that EGCG can inhibit TRAIL-induced apoptosis and activate autophagic flux in cancer cells. However, the mechanism behind these processes is unclear. The present study found that EGCG prevents tumor cell death by antagonizing the TRAIL pathway and activating autophagy flux. Our results indicate that EGCG dose-dependently inhibits TRAIL-induced apoptosis and decreases the binding of death receptor 4 and 5 (DR4 and 5) to TRAIL. In addition, EGCG activates autophagy flux, which is involved in the inhibition of TRAIL cell death. We confirmed that the protective effect of EGCG can be reversed using genetic and pharmacological tools through re-sensitization to TRAIL. The inhibition of autophagy flux affects not only the re-sensitization of tumor cells to TRAIL, but also the restoration of death receptor proteins. This study demonstrates that EGCG inhibits TRAIL-induced apoptosis through the manipulation of autophagic flux and subsequent decrease in number of death receptors. On the basis of these results, we suggest further consideration of the use of autophagy activators such as EGCG in combination anti-tumor therapy with TRAIL.


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