Identification of Antiangiogenic Potential and Cellular Mechanisms of Napyradiomycin A1 Isolated from the Marine-Derived Streptomyces sp. YP127

Angiogenesis is the process of new blood vessel formation. Excessive angiogenesis is a critical factor in the progression of cancer, macular degeneration, and other chronic inflammatory diseases. When investigating the effects of crude extracts of cultured marine microorganisms, an extract of the cu...

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Bibliographic Details
Published in:Journal of natural products (Washington, D.C.) D.C.), 2017-08, Vol.80 (8), p.2269-2275
Main Authors: Hwang, Ji Sun, Kim, Geum Jin, Choi, Hyun Gyu, Kim, Min Cheol, Hahn, Dongyup, Nam, Joo-Won, Nam, Sang-Jip, Kwon, Hak Choel, Chin, Jungwook, Cho, Sung Jin, Hwang, Hayoung, Choi, Hyukjae
Format: Article
Language:English
Subjects:
Angiogenesis Inhibitors - chemistry
Angiogenesis Inhibitors - isolation & purification
Angiogenesis Inhibitors - pharmacology
Cell Proliferation - drug effects
Human Umbilical Vein Endothelial Cells - drug effects
Humans
Molecular Structure
Naphthoquinones - chemistry
Naphthoquinones - isolation & purification
Naphthoquinones - pharmacology
Neovascularization, Pathologic - metabolism
Streptomyces - chemistry
Umbilical Veins - chemistry
Umbilical Veins - physiology
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Summary:Angiogenesis is the process of new blood vessel formation. Excessive angiogenesis is a critical factor in the progression of cancer, macular degeneration, and other chronic inflammatory diseases. When investigating the effects of crude extracts of cultured marine microorganisms, an extract of the cultured Streptomyces sp. YP127 strain was found to inhibit human umbilical vein endothelial cell (HUVEC) tube formation. Bioassay-guided fractionation and spectroscopic data analyses led to the identification of napyradiomycin A1 (1) as an antiangiogenic component of the extract. Compound 1 inhibited HUVEC tube formation in a concentration-dependent manner. It inhibited endothelial cell proliferation but did not affect human dermal fibroblast proliferation. Compound 1 also suppressed migration and invasion of vascular endothelial cells. In addition, compound 1 suppressed vascular endothelial cadherin expression and increased the permeability of the endothelial cell membrane. These results suggested that compound 1 modulates cell permeability and inhibits the angiogenesis of endothelial cells.
ISSN:0163-3864
1520-6025
DOI:10.1021/acs.jnatprod.7b00211