Effects of artesunate on cytokinesis and G₂/M cell cycle progression of tumour cells and budding yeast.

Publication type:
Journal article
Metadata:
Abstract
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.
Addresses
  • Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, Mainz, Germany.
Autoren
eISSN
1790-6245
Externe Identifier
  • PubMed Identifier: 21156967
Open access
false
ISSN
1109-6535
Ausgabe der Veröffentlichung
6
Zeitschrift
Cancer genomics & proteomics
Schlüsselwörter
  • Tumor Cells, Cultured
  • Humans
  • Saccharomyces cerevisiae
  • Artemisinins
  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • Saccharomyces cerevisiae Proteins
  • Repressor Proteins
  • Antimalarials
  • Fluorescent Antibody Technique, Indirect
  • Oligonucleotide Array Sequence Analysis
  • Flow Cytometry
  • Gene Expression Profiling
  • Cell Division
  • Cytokinesis
  • Mitosis
  • G2 Phase
  • Cell Proliferation
  • Ploidies
  • Mad2 Proteins
  • Spindle Apparatus
  • Biomarkers
  • Artesunate
Sprache
eng
Medium
Print
Paginierung
337 - 346
Datum der Veröffentlichung
2010
Status
Published
Datum der Datenerfassung
2010
Titel
Effects of artesunate on cytokinesis and G₂/M cell cycle progression of tumour cells and budding yeast.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
7

Data source: Europe PubMed Central

Other metadata sources:
Abstract
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.
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/21156967
eISSN
1790-6245
Ausgabe der Veröffentlichung
6
Zeitschrift
Cancer Genomics Proteomics
Schlüsselwörter
  • Antimalarials
  • Artemisinins
  • Artesunate
  • Biomarkers
  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • Cell Division
  • Cell Proliferation
  • Cytokinesis
  • Flow Cytometry
  • Fluorescent Antibody Technique, Indirect
  • G2 Phase
  • Gene Expression Profiling
  • Humans
  • Mad2 Proteins
  • Mitosis
  • Oligonucleotide Array Sequence Analysis
  • Ploidies
  • Repressor Proteins
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Spindle Apparatus
  • Tumor Cells, Cultured
Sprache
eng
Country
Greece
Paginierung
337 - 346
PII
7/6/337
Datum der Veröffentlichung
2010
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2011
Titel
Effects of artesunate on cytokinesis and G₂/M cell cycle progression of tumour cells and budding yeast.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
7

Data source: PubMed

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