Triterpenoid Saponins from Acacia victoriae (Bentham) Decrease Tumor Cell Proliferation and Induce Apoptosis

ABSTRACT This report describes the isolation and partial purification of noveltriterpenoid saponins [Fraction 35 (F035)] and two pure biologicallyactive derivatives (termed avicins D and G) from Acacia victoriae, anAustralian desert tree of the Leguminosae family. F035 and the avicinsmarkedly inhibited the growth of several tumor cell lines with minimumgrowth inhibition in human foreskin fibroblasts, mouse fibroblasts, andimmortalized breast epithelial cells at similar concentrations. F035 andthe avicins induced cell cycle (G 1 ) arrest of the human MDA-MB-453breast cancer cell line and apoptosis of the Jurkat (T-cell leukemia) andthe MDA-MB-435 breast cancer cell line. The triterpenoid saponins alsopartially inhibited phosphatidylinositol 3-kinase activity in Jurkat T cellsin a time-dependent manner and phosphorylation in the downstreamprotein Akt, whereas no affect was seen on the Ras/mitogen-activatedprotein kinase cascade. These observations as well as other work from ourlaboratory demonstrating mitochondrial perturbation, chemoprevention,and inhibition of nuclear factor kB suggest that triterpenoid saponinsfrom A. victoriae have potential as novel anticancer agents. Recent worklinking Akt signaling with glucose metabolism, stress resistance, andlongevity suggests other potential applications of these compounds.