Ursolic acid triggers calcium-dependent apoptosis in human Daudi cells

Ursolic acid (UA) is a pentacyclic triterpenoid compound which occurs natur ally in a large variety of vegetarian foods, medicinal herbs and plants. In the present study, ursolic acid was found to decrease cell viability in hu man lymphoma Daudi cells in a dose-dependent manner. UA also induced morpho logical changes in cells as well as loss of membrane asymmetry, DNA fragmen tation and nuclei condensation, indicating that the mechanism by which UA i nduced cell death was through apoptosis. Treatment with UA increased intrac ellular Ca2+ levels. Use of Ca2+ channel inhibitors like verapamil blocked this Ca2+ influx and also the triggering of apoptosis. We hypothesized that the binding of UA to glucocorticoid receptors and the Ca2+ currents induce d constituted the first steps of apoptosis. [(C) 2000 Lippincott Williams & Wilkins].