title: d-Amino Acid Position Influences the Anticancer Activity of Galaxamide Analogs: An Apoptotic Mechanism Study.
abstract: Galaxamide, an extract fromGalaxaura filamentosa, 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.
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou 510632, China. baidf@foxmail.com.
authors.forename: Defa
authors.initials: D
authors.lastname: Bai
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China. siming_yu@hotmail.com.
authors.forename: Siming
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China. zhongsh@stu2014.jnu.edu.cn.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Zhong
authors.affiliation: Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China. zbx840622@163.com.
authors.forename: Bingxin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China. qslhappyrain@gmail.com.
authors.forename: Shaoling
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China. 18826237580@163.com.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China. jignesh.lunagariya@gmail.com.
authors.forename: Jignesh
authors.initials: J
authors.lastname: Lunagariya
authors.affiliation: Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China. tliaoxj@jnu.edu.cn.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Liao
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou 510632, China. txush@jnu.edu.cn.|Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China. txush@jnu.edu.cn.
authors.forename: Shihai
authors.initials: S
authors.lastname: Xu
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C533373:galaxamide
keywords: ">d-amino acid; Galaxamide analogs; anticancer; cyclopeptide; mechanism