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During cell division, microtubles provide the scaffold through which chromosomes are segregated into daughter cells. Thus, the integrity of these structures is critical for cell survival. In addition to this function, microtubules are also involved in other processes such as membrane and intracellular scaffolding, transport secretion, cell adhesion and signaling. Microtubules consist of a heterodimeric mixture of alpha and beta tubulin. These protein complexes aggregate in parallel with one another to form a cylindrical filament (see Figure below). The polymerization and depolymerization of microtubules requires energy and association with a number of other proteins known as MAPs (microtubule associated proteins). Together, these interactions govern the critical steps of chromosome assemble and cell division.  There are a variety of antimicrotubule agents that are used clinically for the treatment of cancer (see below). These drugs differ primarily by the type of microtubule interaction that occurs with each. For example, Taxol and Taxotere belong to the family of compounds known as taxanes. These drugs bind to polymerized microtubules and stabilize the overall structure. This stabilized form resists the necessary step of depolymerization that occurs during mitosis, so the cells remain frozen or arrested at this phase of the cell cycle. Other agents such as the vinca alkaloids act as depolymerizers. These drugs bind to tubulin and prevent the formation of the polymerized microtubule scaffold, thus preventing cells from organizing chromosomes for segregation. In both cases, the sustained disruption of microtubule dynamics ultimately causes cell death. Antimicrotubule drugs are among the most effective drugs for treating cancer. For more information on individual antimicrotubule drugs, please click on the link for each drug below.
Taxanes (Taxol, Taxotere) Other (Estramustine, Epothilone) |
