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

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 (As 2 O 3 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 As 2 O 3 . 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 As 2 O 3 . The mechanism of this growth inhibition was due to the induction of apoptosis. Apoptosis was also induced in fresh ATL cells from patients by As 2 O 3 but far less by RA. As described in patients with acute promyelocytic leukaemia. 1.0 μmol/l of As 2 O 3 can be safely achieved in the serum of patients: however, it is. difficult to maintain this concentration of RA, In conclusion, As 2 O 3 has therapeutic potential for the treatment of ATL and may be far more clinically beneficial than RA.