Green tea polyphenol epigallocatechin-O-gallate induces cell death by acid sphingomyelinase activation in chronic myeloid leukemia cells.
Green tea polyphenol epigallocatechin-O-gallate induces cell death by acid sphingomyelinase activation in chronic myeloid leukemia cells.
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DOI：
10.3892/or.2015.4086
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发表时间：
2015-09
期刊：
影响因子：
4.2
通讯作者：
Tachibana H
中科院分区：
文献类型：
--
作者：
Huang Y;Kumazoe M;Bae J;Yamada S;Takai M;Hidaka S;Yamashita S;Kim Y;Won Y;Murata M;Tsukamoto S;Tachibana H
一项流行病学研究表明，饮用绿茶与降低造血系统恶性肿瘤的风险有关。据报道，主要的绿茶多酚表没食子儿茶素-3-O-没食子酸酯 (EGCG) 具有抗癌作用。慢性粒细胞白血病（CML）是一种主要的造血系统恶性肿瘤，其特征是骨髓细胞扩张。在本研究中，我们展示了 EGCG 诱导的 CML 细胞中的酸性鞘磷脂酶 (ASM) 激活和脂筏聚集。 ASM 抑制剂地昔帕明显着减少 EGCG 诱导的细胞死亡。蛋白激酶 Cδ 是一种众所周知的激酶，在 ASM 激活中发挥重要作用。我们观察到 EGCG 诱导蛋白激酶 Cδ Ser664 磷酸化。重要的是，用可溶性鸟苷酸环化酶抑制剂 NS2028 预处理 CML 细胞后，EGCG 诱导的 ASM 激活显着减少，表明 EGCG 通过环鸟苷酸 (cGMP) 依赖性途径诱导 ASM 激活。事实上，cGMP 阴性调节剂的药理学抑制增强了 EGCG 的抗 CML 作用。这些结果表明 EGCG 通过 cGMP/ASM 途径诱导 CML 细胞死亡。
An epidemiological study showed that green tea consumption is associated with a reduced risk of hematopoietic malignancy. The major green tea polyphenol epigallocatechin-3-O-gallate (EGCG) is reported to have anticancer effects. Chronic myeloid leukemia (CML) is a major hematopoietic malignancy characterized by expansion of myeloid cells. In the present study, we showed EGCG-induced acid sphingomyelinase (ASM) activation and lipid raft clustering in CML cells. The ASM inhibitor desipramine significantly reduced EGCG-induced cell death. Protein kinase Cδ is a well-known kinase that plays an important role in ASM activation. We observed EGCG-induced phos-phorylation of protein kinase Cδ at Ser664. Importantly, EGCG-induced ASM activation was significantly reduced by pretreatment of CML cells with the soluble guanylate cyclase inhibitor NS2028, suggesting that EGCG induced ASM activation through the cyclic guanosine monophosphate (cGMP)-dependent pathway. Indeed, pharmacological inhibition of a cGMP-negative regulator enhanced the anti-CML effect of EGCG. These results indicate that EGCG-induced cell death via the cGMP/ASM pathway in CML cells.