Bioflavonoids commonly and potently induce tyrosine dephosphorylation/inactivation of oncogenic proline-directed protein kinase FA in human prostate carcinoma cells

Anticancer Res. Mar-Apr 1998;18(2A):1117-21.


In this study, we investigate the effect of bioflavonoids on the activity and phosphotyrosine content of oncogenic proline-directed protein kinase FA (PDPK FA) in human prostate carcinoma cells. Chronic treatment of human prostate carcinoma cells with low concentrations of quercetin, apigenin, and kaempferol commonly and potently induced tyrosine dephosphorylation and concurrent inactivated oncogenic PDPK FA in a concentration-dependent manner. This is demonstrated by a specific assay of this kinase's activity in the immunoprecipitates from the cell extracts followed by immunoblotting and phosphotyrosine analysis. The results indicate that bioflavonoids may function as common tyrosine kinase inhibitors to inhibit PDPK FA-specific tyrosine kinase and thereby to induce tyrosine dephosphorylation/inactivation of this oncogenic kinase in human carcinoma cells. Under this condition, quercetin, apigenin, and kaempferol can also inhibit cell growth in a similar concentration-dependent manner. The results further indicate that inhibition of tyrosine phosphorylation/activation of this oncogenic PDPK represents a new mode of action mechanism for bioflavonoids during the antiproliferation process in human carcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Flavonoids / pharmacology*
  • Humans
  • Male
  • Phosphorylation
  • Proline-Directed Protein Kinases
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / pathology
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism*
  • Tyrosine / metabolism*


  • Flavonoids
  • Tyrosine
  • Proline-Directed Protein Kinases
  • Protein-Serine-Threonine Kinases