d-Amino Acid Position Influences the Anticancer Activity of Galaxamide Analogs: An Apoptotic Mechanism Study
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 synth...
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Published in | International journal of molecular sciences Vol. 18; no. 3; p. 544 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
MDPI
10.03.2017
MDPI AG |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1422-0067 1422-0067 |
DOI: | 10.3390/ijms18030544 |