Different microtubule network alterations induced by pachymatismin, a new marine glycoprotein, on two prostatic cell lines

Pachymatismin is a new cytostatic factor extracted from the marine sponge P achymatisma johnstonii Bowerbank. To investigate the mechanism of action of pachymatismin, we studied its effects on two human prostate cell lines (DU 145 and E4) df tumor origin. Immunocytochemistry demonstrated that the drug caused depolymerization of microtubules in DU145 cells, this effect being similar to that of estramustine, known to be a microtubule-depolymerizing a gent. E4 cells, described to be resistant to the microtubule-depolymerizing agent estramustine, were also found resistant to pachymatismin. Pachymatis min at the same dose that destroys microtubule organization in DU145 cells is not able to induce microtubule depolymerization in E4 cells. Compared to the estramustine- and pachymatismin-sensitive DU145 cells, E4 cells reveal ed an increase of beta I+II, beta III, beta IV isotypes as well as posttran slational modifications of tubulin, such as polyglutamylation and acetylati on. In addition, the level of tau protein was also enhanced in E4 cells com pared to DU145 cells. The effects of pachymatismin were tested in vitro usi ng calf brain microtubules. It was shown that the drug lowers the capacity of microtubules to reassemble in vitro. Interestingly, pachymatismin has be en found to inhibit microtubule assembly less efficiently when the ratio of tau to tubulin is increased. Taken together, pachymastismin has been shown to induce in vivo microtubule depolymerization following binding to microt ubule proteins. Changes in microtubule components such as tubulin isoforms or tau may be involved in a decrease of sensitivity to pachymatismin.