Apoptosis inducing activity of viscin, a lipophilic extract from Viscum album L.

Detection of antiproliferative activity and bioactivity-guided fractionation of viscin, a liphophilic extract from Viscum album L., led to the isolation of betulinic acid, oleanolic acid and ursolic acid as active components. Viscin, betulinic acid, oleanolic acid and ursolic acid inhibited growth and induced apoptotic cell death in Molt4, K562 and U937 leukaemia cells. The growth inhibitory effect, of viscin was more pronounced in MoIt4 and U937 cells (IC50 (concentration that inhibited cell proliferation by 50%): 118 +/- 24 and 138 +/- 24 mugmL(-1)) than in K562 cells (IC50: 252 +/- 37 mug mL(-1)). Oleanolic acid was the least effective in allcell lines (7.5-45.5% inhibition at 10 mug mL(-1))and ursolic acid the most active in Molt4 and U937 cells (81.8 and 97.8% inhibition, respectively, at 5 mug mL(-1)). A dose-dependent loss of membrane phospholipid asymmetry associated with apoptosis was induced in all cell lines as shown in flow cytometry by the externalization of phosphaticlylserine and morphological changes in cell size and granularity. There were differences in individual cell lines' response towards the apoptosis-inducing effect of viscin, betulinic acid, oleanolic acid and ursolic acid. The triterpenoids beta-amyrin, beta-amyrinacetate, lupeol, lupeolacetate, beta-sitosterol and stigmasterol, and the fatty acids oleic acid, linoleic acid, palmitic acid and stearic acid were also present in the lipophilic extract.