title: Cytotoxic peptides hemiasterlin, hemiasterlin A and hemiasterlin B induce mitotic arrest and abnormal spindle formation.
abstract: OBJECTIVE
  Hemiasterlin, hemiasterlin A and hemiasterlin B are newly isolated cytotoxic tripeptides with potential as antitumor drugs. We wished to determine their mechanism of cytotoxicity.
  
  
  METHODS
  We studied their effect on cell survival, cell cycle progression, and microtubule morphology in MCF-7 human mammary carcinoma cells.
  
  
  RESULTS
  At the nanomolar concentrations at which they were cytotoxic, the peptides induced arrest in mitotic metaphase. Hemiasterlin A produced abnormal mitotic spindles like those produced by the microtubule inhibitors taxol, nocodazole and vinblastine at low concentrations. At high concentrations hemiasterlin A did not cause microtubule bundling like taxol, but caused microtubule depolymerization like nocodazole and vinblastine.
  
  
  CONCLUSIONS
  The hemiasterlins probably exert their cytotoxic effect by inhibiting spindle microtubule dynamics.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada.
authors.forename: H J
authors.initials: HJ
authors.lastname: Anderson
authors.forename: J E
authors.initials: JE
authors.lastname: Coleman
authors.forename: R J
authors.initials: RJ
authors.lastname: Andersen
authors.forename: M
authors.initials: M
authors.lastname: Roberge
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy; D002453:Cell Cycle / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008387:Marine Toxins / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry*; D008941:Spindle Apparatus / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D008387:Marine Toxins; D009842:Oligopeptides; C103465:hemiasterlin A; C103466:hemiasterlin B; D004121:Dimethyl Sulfoxide