Arsenic trioxide inhibits growth of human T‐cell leukaemia virus type I infected T‐cell lines more effectively than retinoic acids

• Published in: British journal of haematology 1998-12, Vol.103 (3), p.721-728
• Main Authors: Ishitsuka, Kenji, Hanada, Shuichi, Suzuki, Shinsuke, Utsunomiya, Atae, Chyuman, Yoshiko, Takeuchi, Syogo, Takeshita, Taketsugu, Shimotakahara, Sigemi, Uozumi, Kimiharu, Makino, Torahiko, Arima, Terukatsu
• Format: Article
• Language: English
• Subjects: adult T‐cell leukaemia; AIDS/HIV; Antineoplastic agents; Antineoplastic Agents - therapeutic use; apoptosis; Apoptosis - drug effects; Arsenic Trioxide; Arsenicals - therapeutic use; Biological and medical sciences; Cell Division; General aspects; growth inhibition; Hematology; HTLV-I Infections - drug therapy; HTLV-I Infections - pathology; HTLV-I Infections - virology; Human T-lymphotropic virus 1 - growth & development; Humans; Medical sciences; Oxides - therapeutic use; Pharmacology. Drug treatments; retinoic acid; T-Lymphocytes - pathology; T-Lymphocytes - virology; Tretinoin - therapeutic use; Tumor Cells, Cultured
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.1998.01068.x

Adult T‐cell leukaemia (ATL) is difficult to cure using conventional therapies. Recently the therapeutic possibility of retinoic acids (RA) has been reported. In this study, suppression of in vitro growth of human T‐cell leukaemia virus type I (HTLV‐I) infected T‐cell lines and fresh ATL cells by arsenic trioxide (As2O3) were evaluated by comparison with a series of RA derivatives. Proliferation of four HTLV‐I‐infected T‐cell lines was significantly reduced within 72 h by 1.0 μmol/l As2O3. Growth of two out of four HTLV‐I‐infected T‐cell lines was also inhibited by 1.0 μmol/l RA, but to a lesser extent than by As2O3. The mechanism of this growth inhibition was due to the induction of apoptosis. Apoptosis was also induced in fresh ATL cells from patients by As2O3, but far less by RA. As described in patients with acute promyelocytic leukaemia, 1.0 μmol/l of As2O3 can be safely achieved in the serum of patients; however, it is difficult to maintain this concentration of RA. In conclusion, As2O3 has therapeutic potential for the treatment of ATL and may be far more clinically beneficial than RA.