Phenethyl isothiocyanate sensitizes glioma cells to TRAIL-induced apoptosis

Dae-Hee Lee; Dong-Wook Kim; Hai-Chon Lee; Jung-Hyun Lee; Tae-Hwa Lee

doi:10.1016/j.bbrc.2014.01.112

Phenethyl isothiocyanate sensitizes glioma cells to TRAIL-induced apoptosis

Biochem Biophys Res Commun. 2014 Apr 18;446(4):815-21. doi: 10.1016/j.bbrc.2014.01.112. Epub 2014 Jan 31.

Authors

Dae-Hee Lee¹, Dong-Wook Kim², Hai-Chon Lee³, Jung-Hyun Lee⁴, Tae-Hwa Lee⁵

Affiliations

¹ Department of Neurosurgery, University of Virginia, School of Medicine, USA.
² Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, USA.
³ Wide River Institute of Immunology, Seoul National University, Gangwon, Republic of Korea.
⁴ Department of Pediatrics, College of Medicine, Kosin University, Republic of Korea.
⁵ Department of Obstetrics and Gynecology, College of Medicine, Kosin University, Republic of Korea. Electronic address: leehula@hanmail.net.

PMID: 24491546
DOI: 10.1016/j.bbrc.2014.01.112

Abstract

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is a promising antitumor therapy. However, many cancer cells, including malignant glioma cells, tend to be resistant to TRAIL, highlighting the need for strategies to overcome TRAIL resistance. Here we show that in combination with phenethyl isothiocyanate (PEITC), exposure to TRAIL induced apoptosis in TRAIL-resistant glioma cells. Subtoxic concentrations of PEITC significantly potentiated TRAIL-induced cytotoxicity and apoptosis in glioma cells. PEITC dramatically upregulated DR5 receptor expression but had no effects on DR4 receptor. PEITC enhances TRAIL-induced apoptosis through the downregulation of cell survival proteins and the upregulation of DR5 receptors through actions on the ROS-induced-p53.

Keywords: Apoptosis; DR5; PEITC; ROS; TRAIL; p53.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anticarcinogenic Agents / administration & dosage
Anticarcinogenic Agents / pharmacology*
Antineoplastic Combined Chemotherapy Protocols / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Apoptosis / drug effects*
Brain Neoplasms / drug therapy*
Brain Neoplasms / genetics
Brain Neoplasms / metabolism
Cell Line, Tumor
Glioma / drug therapy*
Glioma / genetics
Glioma / metabolism
Humans
Isothiocyanates / administration & dosage
Isothiocyanates / pharmacology*
Reactive Oxygen Species / metabolism
Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics
Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
TNF-Related Apoptosis-Inducing Ligand / administration & dosage
TNF-Related Apoptosis-Inducing Ligand / pharmacology*
Up-Regulation / drug effects

Substances

Anticarcinogenic Agents
Isothiocyanates
Reactive Oxygen Species
Receptors, TNF-Related Apoptosis-Inducing Ligand
TNF-Related Apoptosis-Inducing Ligand
phenethyl isothiocyanate