Zhonghua yi xue za zhi · 1999
[The mechanisms of arsenic trioxide-induced apoptosis in hematopoietic malignant cells].
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Cai X, Chen G, Jia P
Аннотация
OBJECTIVE: To understand if arsenic trioxide (As2O3) is related to the alteration of mitochondrial transmembrane potentials (delta psi m) and its possible mechanisms.
METHODS: Acute promyelocytic leukemia (APL) cell line NB4, chronic lymphoblastic leukemia (CLL) cell line SKW-3, Burkitt's lymphoma cell line Namalwa and other acute myeloid leukemia cell lines HL-60 and U937 were used as in vitro models. The delta psi m was detected by the double staining of propidium iodide (PI) and Rhodamine 123(Rh123), while apoptosis was confirmed by cell viability, sub-G1 cell content as well as gel electrophoresis of genomic DNA and morphological observation. In addition, cellular content of malondialdehyde (MDA) was detected.
RESULTS: In the cells sensitive to As2O3-induced apoptosis, the delta psi m was disrupted with As2O3 treatment. The disulfide-bond reducing agent dithiothreitol (DTT) significantly blocked As2O3-induced delta psi m collapse and apoptosis. For example, with 1 mumol/L As2O3 treatment for 48 hours, PI- Rh123- cells was increased to (16.0 +/- 2.5)%, and DTT simultaneous treatment reduced PI- Rh123- cells and apoptotic cells to (2.9 +/- 0.2)%, and (1.8 +/- 0.3)%, respectively. On the other hand, As2O3 also significantly induced MDA production in NB4(0.479 +/- 0.044, P < 0.01) and SKW-3 (0.168 +/- 0.018) nmol/L, P < 0.01) cells, whereas the effect could not be blocked by DTT.
CONCLUSIONS: The disruption of the delta psi m is the key event of As2O3-induced apoptosis, and the essential mechanisms may be related to the oxidation of thiols; the reactive oxygen species are involved with apoptosis induced by As2O3, but they are not the main points.
METHODS: Acute promyelocytic leukemia (APL) cell line NB4, chronic lymphoblastic leukemia (CLL) cell line SKW-3, Burkitt's lymphoma cell line Namalwa and other acute myeloid leukemia cell lines HL-60 and U937 were used as in vitro models. The delta psi m was detected by the double staining of propidium iodide (PI) and Rhodamine 123(Rh123), while apoptosis was confirmed by cell viability, sub-G1 cell content as well as gel electrophoresis of genomic DNA and morphological observation. In addition, cellular content of malondialdehyde (MDA) was detected.
RESULTS: In the cells sensitive to As2O3-induced apoptosis, the delta psi m was disrupted with As2O3 treatment. The disulfide-bond reducing agent dithiothreitol (DTT) significantly blocked As2O3-induced delta psi m collapse and apoptosis. For example, with 1 mumol/L As2O3 treatment for 48 hours, PI- Rh123- cells was increased to (16.0 +/- 2.5)%, and DTT simultaneous treatment reduced PI- Rh123- cells and apoptotic cells to (2.9 +/- 0.2)%, and (1.8 +/- 0.3)%, respectively. On the other hand, As2O3 also significantly induced MDA production in NB4(0.479 +/- 0.044, P < 0.01) and SKW-3 (0.168 +/- 0.018) nmol/L, P < 0.01) cells, whereas the effect could not be blocked by DTT.
CONCLUSIONS: The disruption of the delta psi m is the key event of As2O3-induced apoptosis, and the essential mechanisms may be related to the oxidation of thiols; the reactive oxygen species are involved with apoptosis induced by As2O3, but they are not the main points.