Paper Synthesis, Cytotoxicity and Apoptosis Induction in Human Tumor Cells by Galaxamide and Its Analogues

Marine Drugs

Xi Xiao¹  Xiaojian Liao¹  Shaoling Qiu¹  Zihao Liu²  Bin Du² 

[1] Department of Chemistry, Life Science School, Jinan University, Guangzhou 510632, China; E-Mails:;Department of Pathology, Medical School, Jinan University, Guangzhou 510632, China; E-Mail:

关键词: galaxamide;    peptide;    synthesis;    anticancer;    apoptosis;   

DOI  :  10.3390/md12084521

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.