Phenethyl isothiocyanate sensitizes glioma cells to TRAIL-induced apoptosis |
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| Authors: | Dae-Hee Lee Dong-Wook Kim Hai-Chon Lee Jung-Hyun Lee Tae-Hwa Lee |
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| Affiliation: | 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 |
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| 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. |
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| Keywords: | PEITC, Phenethyl isothiocyanate ROS, reactive oxygen species NAC, N-acetyl-cysteine PAGE, polyacrylamide gel electrophoresis PARP, poly (ADP-ribose) polymerase PBS, phosphate-buffered saline SDS, sodium dodecyl sulfate TNF, tumor necrosis factor TRAIL, TNF-related apoptosis-inducing ligand |
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