Potent new microtubule stabilizers with unique biochemical and cellular effects show promise for cancer treatment

The taccalonolides are a new class of microtubule stabilizing agents isolated from plants of the genus Tacca. Similar to the effects of the taxanes, the taccalonolides cause microtubule stabilization, leading to the mitotic arrest and death of cancer cells. However, there are several properties of these molecules that suggest they work through a novel mechanism of action, including their ability to form distinct mitotic spindle structures and their propensity to affect interphase microtubules at much lower relative concentrations than the taxanes. The latter finding is of great interest given recent studies suggesting that the anticancer effects of microtubule targeting agents may be due in large part to their interphase effects. Our recent isolation of taccalonolides with potency in the low nanomolar range provided the first indication that these drugs interact directly with tubulin. Intriguingly, the kinetic profile of tubulin polymerization observed in the presence of these potent taccalonolides is unlike that observed with other stabilizers, further suggesting that the taccalonolides interact with tubulin in a manner that is markedly distinct from other classes of microtubule targeting agents. The unique biochemical and cell biological properties of these potent taccalonolides, together with the excellent in vivo antitumor activity observed for this class of agents in drug resistant tumor models, reveal the potential of the taccalonolides as a new class of anticancer drugs.