Inhibition of growth factor signaling pathways by lovastatin

Biochem Biophys Res Commun. 1991 Nov 14;180(3):1284-9. doi: 10.1016/s0006-291x(05)81334-8.

Abstract

Human fibroblasts treated with the antihypercholesterolaemic drug, lovastatin, displayed a diminished signaling response to epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). Supplementing the culture medium with mevalonic acid restored the signaling response. Not all growth factor signaling pathways were impaired, however, as platelet-derived growth factor (PDGF-BB) and basic fibroblast growth factor (bFGF) responses were refractory to lovastatin treatment. These results suggest the involvement of product(s) of mevalonate metabolism (e.g., prenylated proteins such as p21ras or G proteins) in the signal transduction of EGF, insulin and IGF-I. The inhibition of cell growth by lovastatin may be caused by the inability of the cell to enter the S phase of the cell cycle due to obstruction of the signaling of progression factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • DNA Replication / drug effects*
  • Epidermal Growth Factor / pharmacology
  • Fibroblast Growth Factor 2 / pharmacology
  • Gene Expression / drug effects
  • Genes, fos
  • Growth Substances / pharmacology*
  • Humans
  • Infant, Newborn
  • Insulin-Like Growth Factor I / pharmacology
  • Lovastatin / pharmacology*
  • Male
  • Mevalonic Acid / pharmacology
  • Platelet-Derived Growth Factor / pharmacology
  • RNA, Messenger / genetics
  • Signal Transduction / drug effects*
  • Skin
  • Thymidine / metabolism
  • Transcription, Genetic / drug effects

Substances

  • Growth Substances
  • Platelet-Derived Growth Factor
  • RNA, Messenger
  • Fibroblast Growth Factor 2
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I
  • Lovastatin
  • Mevalonic Acid
  • Thymidine