The induction of apoptosis and cell cycle arrest by arsenic trioxide in lymphoid neoplasms

Abstract

Arsenic trioxide (As₂O₃) has recently been shown to induce complete remission in acute promyelocytic leukemia (APL). As₂O₃ reportedly has dose-dependent dual effects on APL cells, triggering apoptosis at relatively high concentrations and inducing differentiation at lower concentrations. However, its effect is still controversial for other AML cells and hematological neoplasms. We studied the in vitro effect of As₂O₃ on lymphoid lineage cells: lymphoma cell lines, NOL-3, Raji and Daudi, a myeloma cell line, NOP-1, normal peripheral blood lymphocytes (PBL), non-Hodgkin's lymphoma (NHL) cells and chronic lymphocytic leukemia (CLL) cells, and compared it with the effect on APL cell line, NB4, as well as other myeloid cell lines, HL-60 and NKM-1. As₂O₃ at a concentration of 1 μmol/l markedly inhibited both proliferation and viability of NB4, NOP-1, NOL-3 and NKM-1 cells, but it reduced only viability in normal PBL, CLL cells and NHL cells. As₂O₃ induced apoptosis and down-regulated bcl-2 expression in NB4, NOP-1 and NKM-1 cells. On the other hand, in HL-60, Raji and Daudi cells, 1 μmol/l As₂O₃ inhibited only the proliferation weakly, and neither induced apoptosis nor down-regulated bcl-2 expression, but arrested only cell cycle at G₁ phase. As₂O₃ at a low concentration of 0.1 μmol/l had no effect on proliferation and viability of these cells except for NB4. These results showed that As₂O₃ exerted variable and definite effects on lymphoid cells and indicated that As₂O₃ might be clinically useful in lymphoid neoplasms such as malignant lymphoma and CLL.