Streptochlorin, a marine natural product, inhibits NF-kappaB activation and suppresses angiogenesis in vitro.
Angiogenesis is an essential step in tumor progress and metastasis. Accordingly, small molecules that inhibit angiogenesis would appear to be a promising way to cure angiogenesis-related diseases, including cancer. In the present study, we report that streptochlorin, a small molecule from marine actinomycete, exhibits a potent antiangiogenic activity. The compound potently inhibited endothelial cell invasion and tube formation stimulated with vascular endothelial cell growth factor (VEGF) at low micromolar concentrations where it showed no cytotoxicity to the cells. In addition, streptochlorin inhibited TNF-alpha-induced NF-kappaB activation in the newly developed cell-based reporter gene assay. These data demonstrate that streptochlorin is a new inhibitor of NF-kappaB activation and can be a basis for the development of novel anti-angiogenic agents.
Chemical Genomics Laboratory, Department of Biotechnology, College of Engineering, Yonsei University, Seoul 120-749, Korea.
In-Kwon
IK
Choi
Hee Jae
HJ
Shin
Hyi-Seung
HS
Lee
Ho Jeong
HJ
Kwon
D039903:Actinobacteria / Q000737:chemistry; D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D007211:Indoles / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010080:Oxazoles / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity
D020533:Angiogenesis Inhibitors; D007155:Immunologic Factors; D007211:Indoles; D016328:NF-kappa B; D010080:Oxazoles; C526070:streptochlorin