Artesunate, a semi-synthetic derivative of artemisinin, is an effective and safe anti-malaria drug, which also exhibits activity towards cancer cells. The present investigation studied the effect of artesunate on the mitosis of cancer and yeast cells by fluorescence microscopy and mRNA microarrays with a focus on the mitotic spindle checkpoint. The cytotoxicity of artesunate towards seven cell lines from six different cancer types was determined using the XTT assay. Furthermore, the cell cycle distribution of artesunate-treated cells was investigated by flow cytometry and immunofluorescence. To elucidate the genes mediating the effect of artesunate in the mitotic spindle checkpoint, knockout mutants of Saccharomyces cerevisiae were generated, since yeast knockouts are easier to generate than knockout strains of mammalian cells. Four out of the seven tested cell lines showed a G₂/M arrest upon artesunate exposure. Cells residing in the G₂/M arrest revealed multiple centrosomes, small multiple spindles and multi-nucleated cells, suggesting a defect in cytokinesis. The mitotic spindle checkpoint genes bub1, bub2, bub3, mad1, mad2 and mad3 were individually deleted and the sensitivity of these mutants towards artesunate was determined by monitoring the cell growth. The Δbub3 and Δmad3 mutants showed an increased sensitivity and the Δmad2 mutant a slightly decreased sensitivity to artesunate in comparison to the respective wild type. Bub3, Mad3 and Mad2 are the main regulators of the mitotic spindle checkpoint, suggesting that artesunate may interfere with this control mechanism.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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