Effect of alisol B acetate, a plant triterpene, on apoptosis in vascular smooth muscle cells and lymphocytes

Glucocorticoid-induced apoptosis is a well-recognized physiological regulat or of T-cell number and function. Alisol B acetate, a triterpene from Alism a Plantago-aquatica, has: a glucocorticoid-like structure, and may have a s imilar function like glucocorticoid-induced apoptosis in both vascular smoo th muscle cell line (A7r5) and human acute lymphoblastic leukemia cell line (CEM cells). For exploring its mechanism, mitochondria membrane potential and apoptosis-related gene expression were discussed. Alisol B (10(-6)-10(- 4) M) inhibited serum-stimulated DNA synthesis in a concentration-dependent manner (IC50 = 4.0 +/- 0.8 X 10(-6) M in A7r5 and 2.1 +/- 1.2 X 10(-6) M i n CEM cells). The cell viability was reduced at 10(-4) M of alisol B. Simil ar results were seen in dexamethasone treatment (a synthetic glucocorticoid , 10(-6) M, 48 h). Apoptosis was induced after the cells were exposed to 10 (-5)-10(-4) M alisol B or 10(-6) M dexamethasone for 48 h. The mitochondria l membrane potential(Delta psi (m)) was significantly reduced after the ali sol B treatment, indicating that the mitochondria might play a role in the alisol B induced cell apoptosis. Alisol B (10(-5)-10(-4) M) increased the l evels of c-myc and bar mRNA and proteins, but not on the anti-apoptotic pro to-oncogene, bcl-2, in A7r5 and CEM cells. In contrast, dexamethasone (10(- 6) M) treatment only caused significant increase in c-myc mRNA levels. Thes e results: suggest that the increased ratio of Bax/Bcl-2 and the decreased mitochondrial membrane potential might be involved in the mechanisms of ali sol B-induced cell apoptosis. (C) 2001 Published by Elsevier Science B.V.