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

Leuk Lymphoma. 2002 May;43(5):1107-14. doi: 10.1080/10428190290021461.

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 micromol/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-alpha 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-alpha receptor independent caspase activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Arsenic Trioxide
  • Arsenicals / pharmacology*
  • Caspases / physiology*
  • Cell Line
  • Enzyme Activation
  • G1 Phase
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy*
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Membrane Potentials / drug effects
  • Oxides / pharmacology*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Receptors, Tumor Necrosis Factor / physiology*
  • T-Lymphocytes / virology
  • Tumor Necrosis Factor-alpha / physiology
  • fas Receptor / physiology*

Substances

  • Antineoplastic Agents
  • Arsenicals
  • Oxides
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Poly(ADP-ribose) Polymerases
  • Caspases
  • Arsenic Trioxide