The epothilone


      The action of the epothilone is focused on the mitosis  : it should prevent from the passage metaphase / anaphase in acting on the microtubules.
      As we have explained it, the dynamic instability of the microtubules is essential for the formation of the mitotic spindle, for the control of the mitosis and for the movement of the chromosomes. In the human cells, the inhibition of this instability by the epothilone may be responsible of the anti-tumor activity. Whereas other medicines lead to the depolymerisation of the microtubules in the cells, in high concentration, the epothilone favours, in the same conditions, the polymerisation and limits the depolymerisation.


      Moreover, other studies have shown that, in low concentrations, the increasing of the rate of polymerisation was not significant, but that the anti-tumor activity was preserved. These data suggest that the increasing of the polymerisation of the microtubules contributes to the no-proliferation of tumor cells, but that this phenomenon is a secondary effect, no essential, in this mechanism.
      Even if it is difficult to explain the role of the dynamic of the microtubules in the metaphase, it is evident that this one suffers some changes during the mitosis. It has been shown that it plays an essential role in the transition metaphase / anaphase. The interaction between the epothilone and the tubulin allows a kinetic stabilisation of the dynamic of the microtubules, and so, a disorganisation of the mitotic spindle during the transition metaphase / anaphase. This interruption of the cell-cycle leads to the apoptosis (cell death), explaining the action of the epothilone. This phenomenon is also principally responsible of this action.
      All these actions are allowed thanks to an interaction between the epothilone and the tubulin by specific settings of fixation.