Sanguinarine as a Potent and Specific Inhibitor of Protein Phosphatase 2C in Vitro and Induces Apoptosis via Phosphorylation of p38 in HL60 Cells
Sanguinarine as a Potent and Specific Inhibitor of Protein Phosphatase 2C in Vitro and Induces Apoptosis via Phosphorylation of p38 in HL60 Cells
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DOI：
10.1271/bbb.90735
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发表时间：
2010-03-01
影响因子：
1.6
通讯作者：
Kimura, Ken-ichi
中科院分区：
文献类型：
--
作者：
Aburai, Nobuhiro;Yoshida, Mami;Kimura, Ken-ichi
血根碱（Sanguinarine）是一种植物生物碱，是一种有效的特异性蛋白磷酸酶（PP）2C抑制剂。它抑制PP 2C竞争性相对于α-酪蛋白（Ki = 0.68 μ M），并显示选择性PP 2C相比，PP 1，PP 2A，PP 2B在体外。在体内，血根碱显示对人早幼粒细胞白血病细胞系HL 60的细胞毒性，IC 50值为0.37 μ M，并通过涉及PP 2C α底物p38磷酸化的caspase-3/7依赖性机制诱导细胞凋亡。p38抑制剂SB 203580可部分抑制血根碱诱导的HL 60细胞凋亡活性，并与p38蛋白磷酸化有关。
Sanguinarine, a plant alkaloid, was identified as a potent and specific protein phosphatase (PP) 2C inhibitor. It inhibited PP2C competitively with respect to alpha-casein (Ki = 0.68 mu M) and showed selectivity for PP2C as compared with PP1, PP2A, and PP2B in vitro. In vivo, sanguinarine showed cytotoxicity toward human promyelocytic leukemia cell line HL60, with an IC50 value of 0.37 mu M, and induced apoptosis through a caspase-3/7-dependent mechanism involving the phosphorylation of p38, a PP2C alpha substrate. The apoptosis activity induced by sanguinarine was partially inhibited by a p38 inhibitor, SB203580, and was involved in the phospho-p38 protein in HL60 cells.