Reference: Li Y, et al. (2007) DH334, a beta-Carboline Anti-Cancer Drug, Inhibits the CDK Activity of Budding Yeast. Cancer Biol Ther 6(8):1193-9

Reference Help

Abstract

The beta-carboline alkaloids present in medicinal plants, such as Peganum harmala and Eurycoma longifolia, have recently drawn attention due to their antitumor activities. Further mechanistic studies indicate that beta-carboline derivatives inhibit DNA topoisomerases and interfere with DNA synthesis. Moreover, some beta-carboline compounds are specific inhibitors of cyclin dependent kinases (CDKs). In this study we used budding yeast as a model system to investigate the antitumor mechanism of beta-carboline drugs. We found that DH334, a beta-carboline derivative, inhibits the growth of budding yeast. Strikingly, deletion of SIC1, which encodes the budding yeast CDK inhibitor, results in resistance to DH334. In contrast, yeast cells defective for Sic1 degradation exhibit morepronounced sensitivity to DH334. The presence of DH334 causes accumulation of yeast cells in G(1) phase, indicating that DH334 blocks cell cycle initiation. We further demonstrated that DH334 inhibits CDK activity as indicated by the decreased phosphorylation of a CDK substrate. All these data suggest that the inhibition of CDK contributes to the toxicity of beta-carboline derivatives to budding yeast. DH334 also inhibits the kinase activity of Cdk2/CyclinA in vitro. Therefore, we speculate that the antitumor activity of beta-carboline drugs could be attributable to their inhibition of CDK.

Reference Type
Journal Article
Authors
Li Y, Liang F, Jiang W, Yu F, Cao R, Ma Q, Dai X, Jiang J, Wang Y, Si S
Primary Lit For
Additional Lit For
Review For

Interaction Annotations

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Type Assay Annotation Action Modification Phenotype Source Reference

Gene Ontology Annotations

Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Gene Ontology Term Qualifier Aspect Method Evidence Source Assigned On Annotation Extension Reference

Phenotype Annotations

Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Regulation Annotations

Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Experiment Assay Construct Conditions Strain Background Reference