Drugs that Stabilize Microtubules

When introduced into cells, microtubule-stabilizing drugs such as taxol, laulimalide, and discodermolide promote polymerization or prevent depolymerization of microtubules.

Taxol binds to specific hydrophobic pockets called taxane pockets at the N-terminal of the β-tubulin subunit. This binding causes a conformational change that increases the lateral affinity between the protofilaments. The conformational change prevents detachment of taxol-bound β-tubulin subunits, further stabilizing and preventing disassembly of microtubules.

When taxol is introduced into a dividing cell, it binds to microtubules in the spindle apparatus and promotes the polymerization and stability of spindle fibers. Spindle fibers lose their dynamic property, and they fail to segregate chromosomes to opposite poles, resulting in mitotic arrest.

Abnormal segregation of chromatids can also trigger induction of apoptosis in tumor cells, thereby enabling the use of taxol to treat cancer.