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

Abstract
Glucocorticoid-induced apoptosis is a well-recognized physiological regulator of T-cell number and function. Alisol B acetate, a triterpene from Alisma Plantago-aquatica, has a glucocorticoid-like structure, and may have a similar function like glucocorticoid-induced apoptosis in both vascular smooth 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 in CEM cells). The cell viability was reduced at 10(-4) M of alisol B. Similar 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 mitochondrial membrane potential (delta psi(m)) was significantly reduced after the alisol 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 levels of c-myc and bax mRNA and proteins, but not on the anti-apoptotic proto-oncogene, bcl-2, in A7r5 and CEM cells. In contrast, dexamethasone (10(-6) M) treatment only caused significant increase in c-myc mRNA levels. These results suggest that the increased ratio of Bax/Bcl-2 and the decreased mitochondrial membrane potential might be involved in the mechanisms of alisol B-induced cell apoptosis.
AuthorsH W Chen, M J Hsu, C T Chien, H C Huang
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 419 Issue 2-3 Pg. 127-38 (May 11 2001) ISSN: 0014-2999 [Print] Netherlands
PMID11426834 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents
  • Cholestenones
  • Enzyme Inhibitors
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • alisol B monoacetate
  • Dexamethasone
  • DNA
Topics
  • Analysis of Variance
  • Animals
  • Anti-Inflammatory Agents (pharmacology)
  • Apoptosis (drug effects)
  • Cell Survival (drug effects)
  • Cells, Cultured
  • Cholestenones (pharmacology)
  • DNA (biosynthesis)
  • Dexamethasone (pharmacology)
  • Enzyme Inhibitors (pharmacology)
  • Flow Cytometry
  • Genes, myc (drug effects)
  • Humans
  • In Situ Nick-End Labeling
  • Lymphocytes (drug effects)
  • Membrane Potentials (drug effects)
  • Muscle, Smooth, Vascular (drug effects)
  • Polymerase Chain Reaction
  • Proto-Oncogene Mas
  • Rats
  • Tumor Cells, Cultured (drug effects)

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