Cytostatic, cytotoxic and protein tyrosine kinase inhibitory activity of ursolic acid in A431 human tumor cells

Anticancer Res. 2000 Nov-Dec;20(6B):4563-70.

Abstract

The effect of the tritepene, ursolic acid, on the proliferation of A431 human epidermoid carcinoma cells was studied. According to our investigations, ursolic acid is a potent inhibitor of A431 cell growth. Ursolic acid markedly reduced A431 cell growth in a time- and dose-dependent manner. We found a good correlation between the results of direct cell counting and the MTT test. During long periods of drug exposure, ursolic acid exhibited both cytotoxic and cytostatic activity. The effect was partially reversible on drug removal. The greatest cytotoxicity was observed both in the trypan blue test and in the MTT test at 50 mM. Investigations on tyrosine kinase inhibition were performed by biochemical and cellular assays on A431 cells. Ursolic acid inhibited tyrosine kinase activity of A431 cells in biochemical assay in a dose-dependent manner with an IC50 of 24 mM. In cellular assay, when A431 cells were pretreated with ursolic acid for 24, 48 and 168 hours at various concentrations (5, 10, 20, 30 and 50 mM), lower values of IC50 were measured: 6.8 microM for 24 hours, 5.2 mM for 48 hours and 1.4 mM for 168 hours. The results suggest that ursolic acid exerts an antiproliferative effect through the inhibition of tyrosine kinase enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Cell Division / drug effects
  • Coloring Agents
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Neoplasm Proteins / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Tetrazolium Salts
  • Thiazoles
  • Time Factors
  • Triterpenes / pharmacology*
  • Tumor Cells, Cultured / drug effects
  • Ursolic Acid

Substances

  • Antineoplastic Agents, Phytogenic
  • Coloring Agents
  • Enzyme Inhibitors
  • Neoplasm Proteins
  • Tetrazolium Salts
  • Thiazoles
  • Triterpenes
  • Protein-Tyrosine Kinases
  • thiazolyl blue