Taxol crystals can masquerade as stabilized microtubules.
Taxol is a potent anti-mitotic drug used in chemotherapy, angioplastic stents, and cell biology research. By binding and stabilizing microtubules, Taxol inhibits their dynamics, crucial for cell division, motility, and survival. The drug has also been reported to induce formation of asters and bundles composed of stabilized microtubules. Surprisingly, at commonly used concentrations, Taxol forms crystals that rapidly bind fluorescent tubulin subunits, generating structures with an uncanny resemblance to microtubule asters and bundles. Kinetic and topological considerations suggest that tubulin subunits, rather than microtubules, bind the crystals. This sequestration of tubulin from the subunit pool would be expected to shift the equilibrium of free to polymerized tubulin to disfavor assembly. Our results imply that some previously reported Taxol-induced asters or bundles could include or be composed of tubulin-decorated Taxol crystals. Thus, reevaluation of certain morphological, chemical, and physical properties of Taxol-treated microtubules may be necessary. Moreover, our findings suggest a novel mechanism for chemotherapy-induced cytotoxicity in non-dividing cells, with far-reaching medical implications.
Foss
Margit
M
Department of Zoology, Oregon State University, Corvallis, Oregon, USA.
Wilcox
Buck W L
BW
Alsop
G Bradley
GB
Zhang
Dahong
D
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D003460:Crystallization; D008870:Microtubules; D017239:Paclitaxel / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel