Phenethyl isothiocyanate sensitizes glioma cells to TRAIL-induced apoptosis.
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.
Department of Neurosurgery, University of Virginia, School of Medicine, USA.
Dae-Hee
DH
Lee
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, USA.
Dong-Wook
DW
Kim
Wide River Institute of Immunology, Seoul National University, Gangwon, Republic of Korea.
Hai-Chon
HC
Lee
Department of Pediatrics, College of Medicine, Kosin University, Republic of Korea.
Jung-Hyun
JH
Lee
Department of Obstetrics and Gynecology, College of Medicine, Kosin University, Republic of Korea. Electronic address: leehula@hanmail.net.
Tae-Hwa
TH
Lee
D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D017382:Reactive Oxygen Species; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C058305:phenethyl isothiocyanate
Apoptosis; DR5; PEITC; ROS; TRAIL; p53