Involvement of p21waf1/cip1 expression in the cytotoxicity of the potent histone deacetylase inhibitor spiruchostatin B towards susceptible NALM-6 human B cell leukemia cells
Involvement of p21waf1/cip1 expression in the cytotoxicity of the potent histone deacetylase inhibitor spiruchostatin B towards susceptible NALM-6 human B cell leukemia cells
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DOI：
10.3892/ijo.2011.1323
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发表时间：
2012-05-01
影响因子：
5.2
通讯作者：
Ishikawa, Masaaki
中科院分区：
文献类型：
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作者：
Kanno, Syu-Ichi;Maeda, Naoyuki;Ishikawa, Masaaki
螺旋体抑素B（SP-B）是一种有效的组蛋白去乙酰化酶（HDAC）抑制剂，在白血病的化疗中具有潜在的应用价值。本研究的目的是研究人白血病细胞系对SP-B的敏感性。我们发现NALM-6人B细胞白血病细胞对SP-B最敏感。HDACI mRNA的表达与白血病细胞HDI易感性呈低度相关。NALM-6的内源性p21（waf/cip 1）mRNA表达高于其他白血病细胞。SP-B诱导的细胞毒性是通过抑制HDAC诱导组蛋白乙酰化介导的，并且SP-B的这种作用与NALM-6细胞中的凋亡相关，凋亡是通过caspase激活介导的。SP-B时间依赖性地增加了亚G1（凋亡）峰的大小，这种效应与SP-B诱导细胞凋亡特征如核形态学变化相关。SP-B在诱导细胞凋亡之前显著增加p21（waf/cip 1）表达。总之，NALM-6细胞，这有一个更高的表达p21（waf/cip 1）mRNA比其他白血病细胞系，是敏感的SP-B诱导的细胞毒性，导致诱导凋亡。我们的研究结果可能是有用的，当建立一个基于SP-B的治疗策略。
Spiruchostatin B (SP-B) is a potent histone deacetylase (HDAC) inhibitor that has potential for the chemotherapy of leukemia. The aim of this study was to study the susceptibility of human leukemia cell lines to SP-B. We found that NALM-6 human B cell leukemia cells are the most susceptible to SP-B. There was a low correlation between the expression of HDACI mRNA and HDI susceptibility of leukemia cells. NALM-6 has higher endogenous p21(waf/cip1) mRNA expression than other leukemia cells. SP-B-induced cytotoxicity was mediated by induction of histone acetylation via inhibition of HDACs, and this effect of SP-B was associated with apoptosis, which was mediated by caspase activation in NALM-6 cells. SP-B time-dependently increased the size of the sub-G1 (apoptotic) peak, and this effect correlated with SP-B induction of cellular apoptotic features such as changes in nuclear morphology. SP-B significantly increased p21(waf/cip1) expression prior to induction of apoptosis. In conclusion, NALM-6 cells, which have a higher expression of p21(waf/cip1) mRNA than other leukemia cell lines, were susceptible to SP-B-induced cytotoxicity that resulted in induction of apoptosis. Our findings may be useful when establishing a therapeutic strategy based on SP-B.