Effect of Arsenic Trioxide in TRAIL (Tumor Necrosis Factor-related Apoptosis Inducing Ligand)-Mediated Apoptosis in Multiple Myeloma Cell Lines.
- Author:
Jae Ho BYUN
1
;
Young Seon HONG
;
Hee Jeong CHEONG
;
Sook Ja KIM
;
Nam Su LEE
;
Jong Ho WON
;
Dae Sik HONG
;
Hee Sook PARK
Author Information
1. St. Mary's Hospital, Division of Oncology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Arsenic trioxide;
Multiple myeloma;
Apoptosis;
Caspase
- MeSH:
Apoptosis*;
Arsenic*;
Caspase 9;
Caspases;
Cell Line*;
Cell Survival;
Multiple Myeloma*;
Necrosis*
- From:Cancer Research and Treatment
2003;35(6):472-477
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: The potential therapeutic application of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), in the treatment of multiple myeloma (MM), was recently proposed. However, there have been some problems with the use of TRAIL, due to the appearance of TRAIL-resistant cells in MM. The effect of arsenic trioxide (As2O3) on the rate of apoptosis induced by TRAIL was evaluated in MM cells. MATERIALS AND METHODS: Using TRAIL-sensitive (RPMI- 8226) and TRAIL-resistant (ARH-77 and IM-9) MM cell lines, the cell viability, induction of apoptosis, and change in the caspases were examined after treatment with TRAIL alone, or in combination with various concentrations of As2O3. RESULTS: Incubating the cell lines with As2O3 augmented the TRAIL-induced apoptosis in the MM cell lines, according to the As2O3 concentration. Apoptosis was mediated through caspase activation. When TRAIL was used alone, caspase8 was activated in the RPMI-8226 cell lines, but not in the ARH-77 and IM-9 cell lines. When As2O3 was added to TRAIL, caspase-9 was activated in the ARH-77 and IM-9 cells. CONCLUSION: The use of As2O3, in combination with TRAIL, would help enhance the level of TRAIL-induced apoptosis, and overcome the TRAIL-resistance, in MM cells.