S. Sangrajrang et al., Different microtubule network alterations induced by pachymatismin, a new marine glycoprotein, on two prostatic cell lines, CANC CHEMOT, 45(2), 2000, pp. 120-126
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.