계명대학교 의학도서관 Repository

β-Lapachone induces programmed necrosis through the RIP1-PARP-AIF-dependent pathway in human hepatocellular carcinoma SK-Hep1 cells

Metadata Downloads
Author(s)
EJ ParkK-j MinT-J LeeYH YooY-S KimTK Kwon
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Cell Death and Disease
Issued Date
2014
Volume
5
Issue
5
Abstract
β-Lapachone activates multiple cell death mechanisms including apoptosis, autophagy and necrotic cell death in cancer cells. In this study, we investigated β-lapachone-induced cell death and the underlying mechanisms in human hepatocellular carcinoma SK-Hep1 cells. β-Lapachone markedly induced cell death without caspase activation. β-Lapachone increased PI uptake and HMGB-1 release to extracellular space, which are markers of necrotic cell death. Necrostatin-1 (a RIP1 kinase inhibitor) markedly inhibited β-lapachone-induced cell death and HMGB-1 release. In addition, β-lapachone activated poly (ADP-ribosyl) polymerase-1(PARP-1) and promoted AIF release, and DPQ (a PARP-1 specific inhibitor) or AIF siRNA blocked β-lapachone-induced cell death. Furthermore, necrostatin-1 blocked PARP-1 activation and cytosolic AIF translocation. We also found that β-lapachone-induced reactive oxygen species (ROS) production has an important role in the activation of the RIP1-PARP1-AIF pathway. Finally, β-lapachone-induced cell death was inhibited by dicoumarol (a NQO-1 inhibitor), and NQO1 expression was correlated with sensitivity to β-lapachone. Taken together, our results demonstrate that β-lapachone induces programmed necrosis through the NQO1-dependent ROS-mediated RIP1-PARP1-AIF pathway.

Keywords: β-Lapachone; NQO1; ROS; RIP1; PARP1; AIF
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
EJ Park et al. (2014). β-Lapachone induces programmed necrosis through the RIP1-PARP-AIF-dependent pathway in human hepatocellular carcinoma SK-Hep1 cells. Cell Death and Disease, 5(5), e1230–e1230. doi: 10.1038/cddis.2014.202
Type
Article
ISSN
2041-4889
DOI
10.1038/cddis.2014.202
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35378
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
공개 및 라이선스
  • 공개 구분공개
파일 목록

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.