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Microtubule-active drugs: mechanism of action and resistance
Dostál, Vojtěch ; Libusová, Lenka (advisor) ; Rösel, Daniel (referee)
Microtubular cytoskeleton represents a target for a myriad of diverse chemical compounds, referred to as microtubule-active drugs. Produced by certain plants, animals or microbes, the substances often effectively elicit cell death - especially in animals and also in plants to a certain extent, but never in species which produce them to defend against their predators. Nowadays, several microtubule-active substances constitute hallmarks of anti-cancer treatment and agricultural weed control. There is an enormous sum of knowledge about the action of paclitaxel (taxol), vinca alkaloids and colchicine, three best-known microtubule active compounds used in medicine, and new research often challenges the previously accepted theories. This work investigates the mechanism of action of microtubule-active drugs from the angle of biochemistry and cell biology, as well as from the physiological standpoint. Effects on microtubule levels and dynamics and the path towards the cell death are reviewed. In the last chapter, attention is given to drug activity in both animal and plant bodies and, finally, to drug-producing plant species which often show substantial resistance.
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