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Cancer Research and Treatment > Volume 35(6); 2003 > Article
Cancer Research and Treatment 2003;35(6): 472-477. doi: https://doi.org/10.4143/crt.2003.35.6.472
Effect of Arsenic Trioxide in TRAIL (Tumor Necrosis Factor-related Apoptosis Inducing Ligand)-Mediated Apoptosis in Multiple Myeloma Cell Lines
Jae Ho Byun, Young Seon Hong, Hee Jeong Cheong, Sook Ja Kim, Nam Su Lee, Jong Ho Won, Dae Sik Hong, Hee Sook Park
1St. Mary's Hospital, Division of Oncology, Department ofInternal Medicine, The Catholic University of Korea, Seoul,Korea.
2Division of Hematology-oncology, Department of InternalMedicine and Institute for Clinical Molecular BiologyResearch, SoonChunHyang University College of Medicine,Seoul, Korea. jhwon@hosp.sch.ac.kr
  Published online: December 31, 2003.
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.
Key words: Arsenic trioxide;Multiple myeloma;Apoptosis;Caspase
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