Cancer Res Treat.  2003 Dec;35(6):472-477.

Effect of Arsenic Trioxide in TRAIL (Tumor Necrosis Factor-related Apoptosis Inducing Ligand)-Mediated Apoptosis in Multiple Myeloma Cell Lines

• Byun JH
• Hong YS
• Cheong HJ
• Kim SJ
• Lee NS
• Won JH
• Hong DS
• Park HS

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.

Keyword

Arsenic trioxide; Multiple myeloma; Apoptosis; Caspase

MeSH Terms

Apoptosis*
Arsenic*
Caspase 9
Caspases
Cell Line*
Cell Survival
Multiple Myeloma*
Necrosis*
Arsenic
Caspase 9
Caspases