Lovastatin inhibits proliferation and differentiation and causes apoptosis in lipopolysaccharide-stimulated murine B cells

Biochem Biophys Res Commun. 1995 Jun 15;211(2):665-70. doi: 10.1006/bbrc.1995.1863.

Abstract

Lipopolysaccharide-stimulated murine B lymphocytes were incubated with the pharmacologic drug lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase at concentrations ranging from 10(-5)-10(-8) M. After 48 hr, treatment with 10(-5)M lovastatin inhibited [3H]thymidine incorporation 55%. Flow cytometric analysis indicated that the fraction of B cells in S phase was reduced from 26.7% +/- 5.44% to 11.6% +/- 2.9% when cells were incubated with 10(-5)M lovastatin. In addition, a large peak appeared to the left of the G1 peak that was indicative of apoptosis in cells treated with 10(-5)M lovastatin. At 96 hr, the number of plaque-forming B cells was decreased 50% in the presence of lovastatin. Together these results suggest that high concentrations of lovastatin can inhibit B cell proliferation and differentiation of murine B lymphocytes in lipopolysaccharide-activated B cells, perhaps through induction of programmed cell death.

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / physiology
  • Cell Cycle / drug effects*
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cells, Cultured
  • DNA / biosynthesis
  • DNA / drug effects
  • Flow Cytometry
  • Hemolytic Plaque Technique
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipopolysaccharides / pharmacology*
  • Lovastatin / pharmacology*
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Depletion
  • Mice
  • Spleen / immunology
  • T-Lymphocytes
  • Thymidine / metabolism

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipopolysaccharides
  • DNA
  • Lovastatin
  • Thymidine