Bai Defa, Yu Siming, Zhong Shenghui, Zhao Bingxin, Qiu Shaoling, Chen Jianwei, Lunagariya Jignesh, Liao Xiaojian, Xu Shihai
College of Pharmacy, Jinan University, Guangzhou 510632, China.
Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
Int J Mol Sci. 2017 Mar 10;18(3):544. doi: 10.3390/ijms18030544.
Galaxamide, an extract from , is a cyclic pentapeptide containing five l-leucines. Due to the particular cyclic structure and the excellent anticancer activity, synthesis of Galaxamide and its analogs and their subsequent bio-applications have attracted great attention. In the present work, we synthesized six Galaxamide analogs by replacing one of the l-leucines with phenylalanine and varying the d-amino acid position. The anticancer effect of the synthesized Galaxamide analogs was tested against four in vitro human cancer cell lines, human hepatocellular cells (HepG₂), human breast cancer cell (MCF-7), human breast adenocarcinoma cells (MDA-MB-435) and a human cervical carcinoma cell line (Hela). Results showed that Galaxamide analogs with different d-amino acid positions displayed distinct anticancer potential. The Galaxamide analog containing d-amino acid at position 5 (Analog-6) presented the strongest anticancer activity. The mechanism study revealed that Analog-6 could cause the early apoptosis of HepG₂ cells by inhibiting their growth in the sub-G1 stage of the cell cycle and induce the chromatin condensation and fragmentation, which can be seen as 68% of HepG₂ cells inhibited in the sub-G1 stage. Moreover, a mitochondria-mediated pathway was found to be involved in the apoptotic process of Analog-6 on HepG₂ cells.
加拉酰胺是一种从……中提取的环五肽，含有五个L-亮氨酸。由于其特殊的环状结构和出色的抗癌活性，加拉酰胺及其类似物的合成以及随后的生物应用受到了极大关注。在本研究中，我们通过用苯丙氨酸取代其中一个L-亮氨酸并改变D-氨基酸位置，合成了六种加拉酰胺类似物。对合成的加拉酰胺类似物针对四种体外人类癌细胞系进行了抗癌效果测试，这四种细胞系分别是人类肝癌细胞（HepG₂）、人类乳腺癌细胞（MCF-7）、人类乳腺腺癌细胞（MDA-MB-435）和一种人类宫颈癌细胞系（Hela）。结果表明，不同D-氨基酸位置的加拉酰胺类似物显示出不同的抗癌潜力。在第5位含有D-氨基酸的加拉酰胺类似物（类似物-6）表现出最强的抗癌活性。机制研究表明，类似物-6可通过抑制HepG₂细胞在细胞周期的亚G1期生长，导致其早期凋亡，并诱导染色质浓缩和碎片化，在亚G1期可观察到68%的HepG₂细胞受到抑制。此外，发现线粒体介导的途径参与了类似物-6对HepG₂细胞的凋亡过程。
