(-)-Agelastatin A is a Potent Modulator of Osteopontin Expression in Normal and Dystrophic Canine Myoblasts

Abstract

(-)-Agelastatin A [(-)-AA] is a naturally occurring alkaloid of marine sponge origin that is a potent modulator of osteopontin. The latter is a multifunctional cytokine expressed in many types of cells and is involved with several important cellular processes, including adhesion, proliferation, immune response stimulation, and so on. As such, modulating OPN could be of therapeutic benefit for various diseases. On that note, (-)-AA has been shown to reduce OPN in xenografted human tumors in nude mice. Additionally, an OPN genotype was associated loss of ambulation in Duchenne muscular dystrophy (DMD) boys and its expression associated with pathology. In this study, we analyzed OPN expression in normal and canine DMD stem cells (myoblasts) after AA treatment. When suspended in 1,2-propanediol (3-deoxy-DL-glycerol), (-)-AA elicited a dose-dependent decrease in OPN mRNA expression in canine DMD myoblasts at doses ranging from 0.01nM – 30nM. There was also a dose-dependent cell detachment after 24 hours of AA treatment with concentrations of 10nM and greater. Further studies are warranted to determine if (-)-AAis safe and can provide therapeutic benefit in animal models of DMD.