Discodermolide, a cytotoxic marine agent that stabilizes microtubules more potently than taxol

Biochemistry. 1996 Jan 9;35(1):243-50. doi: 10.1021/bi9515127.


Computer-assisted structure analysis indicated (+)-discodermolide, a polyhydroxylated alkatetraene lactone marine natural product, was an antimitotic compound, and we confirmed this prediction. Previous work had shown an accumulation of discodermolide-treated cells in the G2/M portion of the cell cycle, and we have now found that discodermolide arrests Burkitt lymphoma cells in mitosis. Discodermolide-treated breast carcinoma cells displayed spectacular rearrangement of the microtubule cytoskeleton, including extensive microtubule bundling. Microtubule rearrangement that occurred with 10 nM discodermolide required 1 microM taxol. Discodermolide had equally impressive effects on tubulin assembly in vitro. Near-total polymerization occurred at 0 degree C with tubulin plus microtubule-associated proteins (MAPs) under conditions in which taxol at an identical concentration was inactive. Without MAPs and/or without GTP, tubulin assembly was also more vigorous with discodermolide than with taxol under every reaction condition examined. Discodermolide-induced polymer differed from taxol-induced polymer in that it was completely stable at 0 degree C in the presence of high concentrations of Ca2+. In a quantitative assay designed to select for agents more effective than taxol in inducing assembly, discodermolide had an EC50 value of 3.2 microM versus 23 microM for taxol.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanes*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms
  • Burkitt Lymphoma
  • Calcium / pharmacology
  • Carbamates*
  • Cell Division / drug effects*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Guanosine Triphosphate / pharmacology
  • Humans
  • Kinetics
  • Lactones / isolation & purification
  • Lactones / pharmacology*
  • Microscopy, Electron
  • Microtubule-Associated Proteins / pharmacology
  • Microtubules / drug effects*
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Paclitaxel / pharmacology*
  • Porifera
  • Pyrones
  • Time Factors
  • Tubulin / drug effects*
  • Tubulin / metabolism
  • Tubulin / ultrastructure
  • Tumor Cells, Cultured


  • Alkanes
  • Antineoplastic Agents
  • Carbamates
  • Lactones
  • Microtubule-Associated Proteins
  • Pyrones
  • Tubulin
  • Guanosine Triphosphate
  • discodermolide
  • Paclitaxel
  • Calcium