Eleutherobin, a novel cytotoxic agent that induces tubulin polymerization, is similar to paclitaxel (Taxol)

Cancer Res. 1998 Mar 15;58(6):1111-5.

Abstract

Eleutherobin is a novel natural product isolated from a marine soft coral that is extremely potent for inducing tubulin polymerization in vitro and is cytotoxic for cancer cells with an IC50 similar to that of paclitaxel. This compound is cross-resistant along with other multidrug-resistant agents against P-glycoprotein-expressing cells and is cross-resistant with paclitaxel against a cell line that has altered tubulin. In mechanistic studies, eleutherobin shares with paclitaxel the ability to induce tubulin polymerization in vitro and is most likely cytotoxic by virtue of this mechanism. Human colon carcinoma cells exposed to eleutherobin contain multiple micronuclei and microtubule bundles, and they arrest in mitosis, depending on concentration, cell line, and length of exposure. These morphological abnormalities appearing in cultured cells are indistinguishable from those induced by paclitaxel. Electron microscopy reveals that eleutherobin induces homogeneous populations of long, rigid microtubules similar to those formed by paclitaxel. Thus, eleutherobin is a new chemotype with a mechanism of action similar to that of paclitaxel and, as such, has promising potential as a new anticancer agent.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Binding Sites
  • Binding, Competitive
  • Cattle
  • Colonic Neoplasms / pathology
  • Diterpenes*
  • Female
  • Growth Inhibitors / pharmacology
  • Humans
  • Microtubules / drug effects*
  • Ovarian Neoplasms / pathology
  • Paclitaxel / pharmacology
  • Polymers
  • Tubulin / metabolism
  • Tumor Cells, Cultured

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Diterpenes
  • Growth Inhibitors
  • Polymers
  • Tubulin
  • eleutherobin
  • Paclitaxel