Goniodomin A, an antifungal polyether macrolide, exhibits antiangiogenic activities via inhibition of actin reorganization in endothelial cells

Abstract

Goniodomin A (GDA) is an antifungal polyether macrolide isolated from the dinoflagellate Goniodoma pseudogoniaulax. Previous studies revealed that GDA profoundly affected cytoskeletal reorganization. We examined the effect of GDA on the angiogenic properties of vascular endothelial cells. GDA itself did not affect proliferation of, migration of, and tube formation in type I collagen gels by, bovine aortic endothelial cells (BAECs). Proliferation of BAECs stimulated by bFGF was not affected by GDA at concentrations of up to 10 nM. However, at similar concentrations, GDA significantly inhibited bFGF-induced migration and tube formation in type I collagen gels by BAECs. Actin reorganization is required for cell migration. GDA caused the perinuclear aggregation of filamentous actin and inhibited stress fiber formation in bFGF- or VEGF-stimulated BAECs and lysophosphatidic acid-stimulated HeLa cells. However, GDA did not affect stress fiber structures already formed through Gbetagamma expression or in constitutively active RhoA mutant HeLa cells. Finally, GDA inhibited forming of vasucular system in a chorioallantoic membrane. Our results indicated that GDA suppressed angiogenic properties of ECs at least in part through the inhibition of actin reorganization and inhibited angiogenesis in vivo.

Basic fibroblast growth factor induces cholangiocarcinoma cell migration via activation of the MEK1/2 pathway

“…In this study, the treatment of cholangiocarcinoma cells with bFGF increased actin polymerization formation and cell migration. These findings are consistent with a previous study demonstrating that bFGF induced stress fiber formation in cancer cells (18). Taken together, these observations suggest that bFGF induces cholangiocarcinoma cell migration via the regulation of actin organization.…”

Production of goniodomin A by the planktonic, chain-forming dinoflagellate Alexandrium monilatum (Howell) Balech isolated from the Gulf Coast of the United States

“…Pharmacological research carried out on this substance indicated that goniodomin A has extreme effects on the reorganization of the cytoskeleton. Abe et al (2002) found that this compound inhibited angiogenic properties of endothelial cells partly by inhibition of actin reorganization. The findings from Furukawa et al (1993) suggested that goniodomin A causes a conformational change resulting in an enhancement of actomyosin ATPase activity at concentration < 10 À6 M, but conformational changes at concentrations > 10 À6 M may lead to a loss of ATPase activity in rabbit skeletal muscle.…”

Fibroblast Growth Factors/Fibroblast Growth Factor Receptors as Targets for the Development of Anti-Angiogenesis Strategies

“…Similarly, microtubule-stabilizing agents, including paclitaxel and taxane derivatives [127,128], affect FGF2-triggered angiogenesis in vitro and in vivo. Also, by preventing the formation of stress fibers, the antifungal polyether macrolide goniodomin-A inhibits FGF2-induced migration and morphogenesis in ECs, leaving unaffected their proliferation [129]. These findings are of importance [240], angiogenesis [241], EC monolayer wound repair a proliferation [240] angiogensis [241] morphogenesis, angiogenesis [242] proliferation, angiogenesis [243] PD 098059 U0126 apigenin ERK1/2…”