Synthesis, cytotoxicity and apoptosis induction in human tumor cells by galaxamide and its analogues [corrected].
Synthesis, cytotoxicity and apoptosis induction in human tumor cells by galaxamide and its analogues [corrected].
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论文 佳拉沙酰胺及其类似物的合成、细胞毒性和诱导人肿瘤细胞凋亡
DOI：
10.3390/md12084521
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发表时间：
2014-08-18
期刊：
影响因子：
5.4
通讯作者：
Xu S
中科院分区：
文献类型：
--
作者：
Xiao X;Liao X;Qiu S;Liu Z;Du B;Xu S
我们前期的研究报道了从丝状乳藻中提取的含五个亮氨酸的环五肽Galaxamide具有显著的抗癌细胞毒性。这种新型的环肽为结构修饰提供了新的骨架，用于寻找具有更好抗癌性能的新药。本研究通过添加一个新的氨基酸苯丙氨酸来改变d/l氨基酸的数目，合成了五个类似物。Galaxamide和它的五个类似物通过MTT法进行评估，以检查它们的细胞毒活性。我们发现，修饰的类似物5，这是指A5，显示对每个测试的细胞系的广谱细胞毒活性;此外，A5的IC 50低于galaxamide和其他类似物。此外，我们使用流式细胞术和蛋白质印迹分析来研究加来沙胺和A5是否可以诱导癌细胞凋亡。流式细胞术的研究表明，不同浓度的galaxamide或A5处理72小时以上的HepG 2细胞表现出显着的和剂量依赖性的早期凋亡细胞的百分比增加。Western blotting结果显示，两种化合物均通过caspase介导的途径诱导HepG 2细胞凋亡。研究结果表明，加来沙胺及其类似物具有作为临床抗癌药物的潜在应用价值。
Our previous study reported that galaxamide, which is a cyclo-pentapeptide containing five leucines that was extracted from Galaxaura filamentosa, displayed remarkable anticancer cytotoxicity. This novel cyclo-peptide provided a new skeleton for the structural modifications used in finding new drugs with better anticancer properties. In this study, five analogues were synthesized based on changing the number of d/l amino acids by adding a new amino acid, phenylalanine. Galaxamide and five of its analogues were evaluated through MTT assays to examine their cytotoxic activities. We found that modified analogue 5, which is referred to as A5, displayed broad spectrum cytotoxic activity toward every cell line tested; in addition, the IC50 of A5 was lower than that of galaxamide and the other analogues. Furthermore, we used flow cytometry and western blot assays to investigate whether galaxamide and A5 could induce cancer cell apoptosis. The flow cytometric studies showed that HepG2 cells treated with different concentrations of galaxamide or A5 over 72 h displayed significant and dose-dependent increases in the percentages of early-stage apoptotic cells. Western blotting revealed that both compounds induce caspase-dependent apoptosis in HepG2 cells through a mitochondria-mediated pathway. The results demonstrate that galaxamide and its analogues have potential applications as clinical anticancer drugs.
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影响因子：
56.9
作者：
Pan, GH;ORourke, K;Dixit, VM
通讯作者：
Dixit, VM
影响因子：
1.8
作者：
Belofsky, GN;Jensen, PR;Fenical, W
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Fenical, W
影响因子：
5.2
作者：
Xu, Wen-Jie;Liao, Xiao-Jian;Pan, Shan-Shan
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Pan, Shan-Shan
影响因子：
5.2
作者：
Davis, Melinda R.;Styers, Thomas J.;McAlpine, Shelli R.
通讯作者：
McAlpine, Shelli R.
影响因子：
16.6
作者：
Zhu, JD;Ma, DW
通讯作者：
Ma, DW