Triterpenoid saponins from Acacia victoriae (Bentham) decrease tumor cell proliferation and induce apoptosis

This report describes the isolation and partial purification of novel trite rpenoid saponins [Fraction 35 (F035)] and two pure biologically active deri vatives (termed avicins D and G) from Acacia victoriae, an Australian deser t tree of the Leguminosae family. F035 and the avicins markedly inhibited t he growth of several tumor cell lines with minimum growth inhibition in hum an foreskin fibroblasts, mouse fibroblasts, and immortalized breast epithel ial cells at similar concentrations, F035 and the avicins induced cell cycl e (G(1)) arrest of the human MDA-MB-453 breast canter cell line and apoptos is of the Jurkat (T-cell leukemia) and the MDA-MB-435 breast cancer cell Li ne. The triterpenoid saponins also partially inhibited phosphatidylinositol 3-kinase activity in Jurkat T cells in a time-dependent manner and phospho rylation in the downstream protein Akt, whereas no affect was seen on the R as/mitogen-activated protein kinase cascade. These observations as well as other work from our laboratory demonstrating mitochondrial perturbation, ch emoprevention, and inhibition of nuclear factor kappaB suggest that triterp enoid saponins from A. victoriae have potential as novel anticancer agents. Recent work linking Akt signaling with glucose metabolism, stress resistan ce, and longevity suggests other potential applications of these compounds.