Anti-tumor promoting effects of palmitoyl: protein thioesterase inhibitors against a human neurotumor cell line
Anti-tumor promoting effects of palmitoyl: protein thioesterase inhibitors against a human neurotumor cell line
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DOI：
10.1016/s0304-3835(02)00403-2
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发表时间：
2002-12-10
期刊：
影响因子：
9.7
通讯作者：
Dawson, PE
中科院分区：
文献类型：
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作者：
Dawson, G;Dawson, SA;Dawson, PE
抑制蛋白质的脱氨基转移会扰乱肿瘤细胞中的细胞生存信号，导致细胞死亡增加。我们化学合成了一种棕榈酰半胱氨酸硫酯键的非水解性类似物(ACG-α-酮酰胺-棕榈酰二氨基丙酸酯-VKIKK)(DAPKA)，并在体外用基于荧光的(4-methylumbelliferyl-beta-gluco-6-thiopalmitate)方法检测了它对棕榈酰基：蛋白硫酯酶的抑制作用。然后我们证明了它可以杀死培养的肿瘤细胞，并通过化疗药物如依托泊苷和阿霉素增强对神经肿瘤细胞的杀伤作用。PPT1的过表达对依托泊苷和酮胺诱导的细胞凋亡有保护作用，且两者的抑制作用是相加的。(C)2002爱思唯尔科学爱尔兰有限公司。保留所有权利。
Inhibiting the depalmitoylation of proteins disrupts cell survival signaling in tumor cells and leads to increased cell death. We chemically synthesized a non-hydrolyzable analog of the palmitoyl-cysteine thioester linkage (AcG-alpha-ketoamido-palmitoyl diamino propionate-VKIKK) (DAPKA) and showed that it inhibits palmitoyl:protein thioesterase (PPTI) in an in vitro assay using a specific fluorescent-based (4-methylumbelliferyl-beta-gluco-6-thiopalmitate) assay. We then showed that it killed cultured tumor cells and enhanced the killing of neurotumor cells by chemotherapeutic drugs such as etoposide and adriamycin. Overexpression of PPT1 protected against apoptosis induced by etoposide and the ketoamide and the inhibitory effect of the two was additive. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.