Antimitotic and antitubulin activity of the tumor inhibitor steganacin

Abstract

Steganacin, a newly isolated tumor inhibitor, completely inhibits cleavage in sea urchin eggs at 3 X 10(-7) M by preventing the formation of the mitotic apparatus. Steganacin inhibits the polymerization of tubulin in vitro and also causes a slow depolymerization of preformed microtubules. Optical ultracentrifuge studies of steganacin-treated tubulin show a small reduction in 20 S and 30 S peaks at 0 degree. In electron microscope studies the ring structure of tubulin is seen at 0 degree but disappears if the temperature of tubulin incubated with steganacin is raised to 37 degrees. Steganacin inhibits the binding of colchicine to tubulin and thus resembles podophyllotoxin, which also competitively inhibits colchicine binding. Steganacin had a trimethoxybenzene ring and probably interacts with that portion of the colchicine-binding site that recognizes the trimethoxybenzene ring of colchicine.