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.