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

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.

Cell cycle arrest and growth inhibition by the protein kinase antagonist UCN-01 in human breast carcinoma cells.

UCN-01 is a derivative of staurosporine, initially developed as a potentially selective inhibitor of the Ca(2+)- and phospholipid-dependent protein kinase C, but with the capacity to inhibit a number of tyrosine and serine/threonine kinases. UCN-01 inhibits the growth of 5 breast carcinoma cell lines with a 50% inhibitory concentration range of 30-100 nM during 6 days of continuous exposure. In MCF-7, MDA-MB453, and SK-BR-3 cells, UCN-01 is 5-fold more potent in growth inhibition than its diastereomer UCN-02, but the 2 compounds are equipotent in the inhibition of MDA-MB468 and H85787 cell growth.

Growth inhibition with reversible cell cycle arrest of carcinoma cells by flavone L86-8275.

Background: Previous studies have shown that polyhydroxylated flavonoids such as quercetin and genistein can inhibit tumor cell growth in vitro, and preliminary in vivo studies of the flavone L86-8275 have shown growth inhibition of LX529 and A549 lung carcinomas. L86-8275 [(-)cis-5,7-dihydroxy-2-(2-chlorophenyl)-8[4-(3-hydroxy-1-methyl)- piperidinyl]-4H-1-benzopyran-4-one] is a flavone of novel structure.

Purpose: The purpose of this study was to determine in vitro whether L86-8275 is a more potent inhibitor of growth in breast carcinoma and lung carcinoma cells than quercetin or genistein.

Synergistic antiproliferative effects of the combination of interleukin-1 alpha and doxorubicin against human melanoma cells.

We have investigated the antiproliferative effects of recombinant human interleukin-1 alpha (IL-1) combined with the cytotoxic antitumor drug doxorubicin against A375 human melanoma IL-1-sensitive (C6) and IL-1-resistant (C5) clonal cell lines. Growth inhibition was assessed by the MTT assay, and C5 cells were 10-fold less sensitive to IL-1 than the C6 cells, but both cell lines were equally sensitive to doxorubicin. Synergistic antitumor activity between the two agents was evaluated by median effects/combination index analysis, and IL-1 and doxorubicin were strongly synergistic over a broad range of drug concentrations.