Microtubule inhibitor podophyllotoxin

However, in 1942 it was removed from U. S. pharmacopeia because of its severe gastrointestinal toxicity. Currently, it still remains as an effective therapy for treatment of venereal warts [25]. Furthermore, podophyllotoxin and its derivatives have been extensively studied in the last 60 years for their powerful antitumor effects. Podophyllotoxin itself is a powerful microtubule inhibitor. Microtubules are tubular polymers whose protomeric unit (a and 3-tubulin) forms an heterodimer and are the dynamic constituents of the cytoskeleton. The cytoplasm of eukaryotic cells contains a soluble pool of unpolymerised tubulin protomers as well as an organised array of microtubules. Microtubules can be rapidly assembled or disassembled in response to various stimuli with little or no change in the total amount of tubuline. Cytoplasmatic microtubules are... 

Taxol is a diterpene alkaloid isolated as an anticancer agent from the bark of T. brevifolia [1]. Subsequently, it was reported that this alkaloid possessed clinical effects for the treatment of leukemia and had excellent efects on refractory ovarian and mammary cancer. The mechanism of action of this alkaloid is to promote the formation of microtubules, the opposite action to that of the microtubule inhibitors hke podophyllotoxin, colchicine, and vinblastine [2,3]. 

The determination of the mechanism of action of Taxol proved to be very important in the clinical development of this cytotoxic agent. Initial studies demonstrated that it was a mitotic spindle inhibitor. However, subsequent studies demonstrated that the mechanism was unique because it stabilized microtubules and prevented their depolymerization back to tubulin, an effect opposite that of other antimitotic agents as colchicine, vincristine, vinblastine, and podophyllotoxin. ... 

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