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Title: Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells

Abstract

Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS). We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy. - Highlights: • Most GBM cells have been reported to be resistant to TRAIL-induced apoptosis. • Gingerol enhances the expression level of anti-apoptotic proteins by ROS. • Gingerol enhancesmore » TRAIL-induced apoptosis through actions on the ROS–Bcl2 pathway.« less

Authors:
 [1];  [2];  [3];  [1];  [4]
  1. Departments of Surgery and Pharmacology and Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA (United States)
  2. Department of Microbiology, Immunology, and Cancer Biology, University of VA (United States)
  3. Division of Metabolism and Functionality Research, Korea Food Research Institute (Korea, Republic of)
  4. School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22439823
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 279; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADULTS; APOPTOSIS; BRAIN; CLINICAL TRIALS; GLIOMAS; OXYGEN; RADIOPROTECTIVE SUBSTANCES; RECEPTORS; SPICES; THERAPY

Citation Formats

Lee, Dae-Hee, E-mail: leedneo@gmail.com, Kim, Dong-Wook, Jung, Chang-Hwa, Lee, Yong J., and Park, Daeho, E-mail: daehopark@gist.ac.kr. Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells. United States: N. p., 2014. Web. doi:10.1016/J.TAAP.2014.06.030.
Lee, Dae-Hee, E-mail: leedneo@gmail.com, Kim, Dong-Wook, Jung, Chang-Hwa, Lee, Yong J., & Park, Daeho, E-mail: daehopark@gist.ac.kr. Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells. United States. doi:10.1016/J.TAAP.2014.06.030.
Lee, Dae-Hee, E-mail: leedneo@gmail.com, Kim, Dong-Wook, Jung, Chang-Hwa, Lee, Yong J., and Park, Daeho, E-mail: daehopark@gist.ac.kr. Mon . "Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells". United States. doi:10.1016/J.TAAP.2014.06.030.
@article{osti_22439823,
title = {Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells},
author = {Lee, Dae-Hee, E-mail: leedneo@gmail.com and Kim, Dong-Wook and Jung, Chang-Hwa and Lee, Yong J. and Park, Daeho, E-mail: daehopark@gist.ac.kr},
abstractNote = {Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS). We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy. - Highlights: • Most GBM cells have been reported to be resistant to TRAIL-induced apoptosis. • Gingerol enhances the expression level of anti-apoptotic proteins by ROS. • Gingerol enhances TRAIL-induced apoptosis through actions on the ROS–Bcl2 pathway.},
doi = {10.1016/J.TAAP.2014.06.030},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 279,
place = {United States},
year = {2014},
month = {9}
}