Arsenic Trioxide Induces Apoptosis in HTLV-I Infected T-cell Lines and Fresh Adult T-cell Leukemia Cells Through CD95 or Tumor Necrosis Factor α Receptor Independent Caspase Activation

Abstract

Arsenic trioxide (As₂O₃) has been reported to induce apoptosis in human T-cell leukemia virus type-I (HTLV-I) infected T-cell lines and fresh adult T-cell leukemia (ATL) cells and to induce G₁ phase accumulation in HTLV-I infected T-cell lines. The present study aimed to clarify the pathway of As₂O₃-induced apoptosis in HTLV-I infected T-cell lines, MT-1 and MT-2, and fresh ATL cells separated from peripheral blood of patients with acute or chronic type ATL. Cells were treated up to 72 h at clinically tolerable concentrations of As₂O₃ (1–2 µmol/l) shown to be safe in patients with acute promyelocytic leukemia (APL). Activation of caspases 3, 8, and 9, loss of mitochondrial transmembrane potential and cleavage of poly (adenosine diphosphate-ribose) polymerase (PARP) were observed during As₂O₃ treatment. Furthermore, prior exposure to a broad-spectrum caspase inhibitor blocked As₂O₃-induced apoptosis but not G₁ phase accumulation. While pre-treatment with a CD95 receptor-blocking antibody (Ab) or a TNF-α neutralizing Ab did not show such inhibitions in these cells. In conclusion, As₂O₃ induces apoptosis in HTLV-I infected T-cell lines and fresh ATL cells through CD95 or TNF-α receptor independent caspase activation.

• ATL
• As₂O₃
• Apoptosis
• Caspase
• CD95
• TNF-α receptor