Arsenic trioxide and interferon-alpha synergize to induce cell cycle arrest and apoptosis in human T-cell lymphotropic virus type I-transformed cells.
Human T-cell lymphotropic virus type I (HTLV-I) is the causative agent of adult T-cell leukemia/lymphoma (ATL). ATL is an aggressive proliferation of mature activated T cells associated with a poor prognosis. The combination of the antiviral agents, zidovudine (AZT) and interferon (IFN), is a potent treatment of ATL. Recently, arsenic trioxide (As) was shown to be an effective treatment of acute promyelocytic leukemia (APL). We have tested the effects of the combination of As and IFN on cell proliferation, cell cycle phases distribution, and apoptosis in ATL-derived or control T-cell lines. A high synergistic effect between IFN and As was observed in ATL-derived cell lines in comparison to the control cell lines, with a dramatic inhibition of cell proliferation, G1 arrest, and induction of apoptosis. Similar results were obtained with fresh leukemia cells derived from an ATL patient. Although the mechanisms involved are unclear, these results could provide a rational basis for combined As and IFN treatments in ATL.
Bazarbachi
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A
Departments of Internal Medicine and Biochemsitry, Human Morphology, and Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon. bazarbac@aub.edu.lb
El-Sabban
M E
ME
Nasr
R
R
Quignon
F
F
Awaraji
C
C
Kersual
J
J
Dianoux
L
L
Zermati
Y
Y
Haidar
J H
JH
Hermine
O
O
de Thé
H
H
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002478:Cells, Cultured; D004357:Drug Synergism; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D010087:Oxides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000096:biosynthesis
D000970:Antineoplastic Agents; D001152:Arsenicals; D016898:Interferon-alpha; D010087:Oxides; D014764:Viral Proteins; D000077237:Arsenic Trioxide