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.

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.

• Authors: Kenji Ishitsuka, Ryuji Ikeda, Atae Utsunomiya, Kimiharu Uozumi, Shuichi Hanada, Shinsuke Suzuki, Shogo Takeuchi, Yoshifusa Takatsuka, Taketsugu Takeshita, Nobuhito Ohno, Terukatsu Arima
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 43 Issue 5 Pg. 1107-14 (May 2002) ISSN: 1042-8194 [Print] United States
• PMID: 12148893 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, 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)