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The induction of apoptosis and cell cycle arrest by arsenic trioxide in lymphoid neoplasms.
- Source :
-
Leukemia [Leukemia] 1998 Sep; Vol. 12 (9), pp. 1383-91. - Publication Year :
- 1998
-
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 micromol/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 micromol/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 micromol/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.
- Subjects :
- Arsenic Trioxide
Cell Division drug effects
Cell Survival drug effects
DNA Fragmentation
DNA, Neoplasm
Humans
Proto-Oncogene Proteins c-bcl-2 metabolism
Tumor Cells, Cultured drug effects
Antineoplastic Agents pharmacology
Apoptosis drug effects
Arsenicals pharmacology
Interphase drug effects
Leukemia, Lymphocytic, Chronic, B-Cell metabolism
Leukemia, Lymphocytic, Chronic, B-Cell pathology
Lymphoma, Non-Hodgkin metabolism
Lymphoma, Non-Hodgkin pathology
Oxides pharmacology
Proto-Oncogene Proteins c-bcl-2 drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0887-6924
- Volume :
- 12
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Leukemia
- Publication Type :
- Academic Journal
- Accession number :
- 9737686
- Full Text :
- https://doi.org/10.1038/sj.leu.2401112