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Biochem Pharmacol. 1993 Nov 17;46(10):1831-40.

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

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Laboratory of Biological Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.


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.

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