Alteration of the phosphorylation state of p34cdc2 kinase by the flavone L86-8275 in breast carcinoma cells. Correlation with decreased H1 kinase activity

Biochem Pharmacol. 1993 Nov 17;46(10):1831-40. doi: 10.1016/0006-2952(93)90590-s.


The flavone L86-8275 [(-)cis-5,7-dihydroxy-2-(2-chlorophenyl)-8-[4-(3-hydroxy-1-methyl)- piperidinyl]-4H-1-benzopyran-4-one] delayed the progression of aphidicolin-synchronized MDA-468 breast carcinoma cells through S phase and prevented progression through G2. L86-8275 prevented the G2-related increase in histone H1 kinase activity mediated by cyclin-dependent kinase-1 (p34cdc2 kinase). L86-8275 inhibited [32P]orthophosphate labeling of p34cdc2 threonine and tyrosine residues and decreased the phosphotyrosine content of p34cdc2. Diminution of p34cdc2 phosphotyrosine appeared selective, as a general depletion of cellular phosphotyrosine was not observed. The mass of p34cdc2 in L86-8275-exposed cells was not decreased during the period over which these effects occurred. [35S]Methionine labeling of p34cdc2 or other cellular proteins was not inhibited at concentrations that were effective for complete cellular growth inhibition. We hypothesize that L86-8275 interferes with the normal cell cycle-dependent phosphorylation of p34cdc2, resulting in decreased kinase activity and cell cycle arrest.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Aphidicolin
  • Breast Neoplasms / enzymology*
  • CDC2 Protein Kinase / metabolism*
  • Cyclins / biosynthesis
  • Cycloheximide / pharmacology
  • Down-Regulation
  • Emetine / pharmacology
  • Enzyme Activation / drug effects
  • Flavonoids / pharmacology*
  • Humans
  • Maturation-Promoting Factor / metabolism*
  • Mitosis / drug effects
  • Molecular Sequence Data
  • Phosphorylation / drug effects
  • Piperidines / pharmacology*
  • Precipitin Tests
  • S Phase
  • Tumor Cells, Cultured / drug effects


  • Cyclins
  • Flavonoids
  • Piperidines
  • Aphidicolin
  • alvocidib
  • Cycloheximide
  • CDC2 Protein Kinase
  • Maturation-Promoting Factor
  • Emetine