Taxol

Taxol (Paclitaxel), MW 854

Source

Taxol (Paclitaxel) is produced by the Pacific Yew (Taxus baccata) and is widely used for cancer therapy, because it blocks mitosis. Chemical synthesis, although principally successful, is not economically feasible, production in cell culture was not efficient. Taxol derives from the terpenoid pathway, precursor is geranyl-geranyl diphosphate.

Mode of action

Taxol binds to beta-tubulin and inhibits the dissociation of microtubules. The affinity constant is around 1 µM, one taxol molecule binds one beta-tubulin unit. Due to the blocked disassembly, a net stabilisation of microtubules results, very often accompanied by bundling of microtubules. The medical effect is based on arrest of mitosis due to impaired spindle breakdown in anaphase.

Practical aspects

Taxol (Paclitaxel) is well soluble in methanol, typical working concentrations are 1-20 µM, stock is around the 500 - 1000 fold concentration. Keep at -20°C.

Literature

  • Leistner E (2005) Die Biologie der Taxane. Pharmazie in unserer Zeit 34, 98–103 (in German, biology of taxol, discovery and pharmaceutical use) - pdf
  • Parness J, Horwitz SB (1981) Taxol Binds to Polymerized Tubulin In Vitro. J Cell Biol 91, 479-487 (binding site) - pdf

Publications from our group using Taxol

 

93. Zaban B, Maisch J, Nick P (2013) Dynamic actin controls polarity induction de novo in protoplasts, J Int Plant Biol 55, 142–159

98. Liu Q, Qiao F, Ismail A, Chang X, Nick P (2013) The Plant Cytoskeleton Controls Regulatory Volume Increase. BBA Membranes 1828, 2111–2120

92. Krtková J, Zimmermann A, Schwarzerová K, Nick P (2012) Hsp90 binds microtubules and is involved in the reorganization of the microtubular network in angiosperms. J Plant Physiol 169, 1329-1339

81. Qiao F, Chang X, Nick P (2010) The cytoskeleton enhances gene expression in the response to the Harpin elicitor in grapevine. J Exp Bot. 61, 4021-4031

57. Gutjahr C, Nick P (2006) Acrylamide inhibits gravitropism and destroys microtubules in rice coleoptiles. Protoplasma 227, 211-222

38. Pay A, Resch K, Frohnmeyer H, Nagy F, Nick P (2002) RanGAP1 is localized in the nuclear envelope and the phragmoplast. Plant J 30, 699-710

42. Abdrakhamanova A, Wang QY, Khokhlova L, Nick  (2003). Is microtubule assembly a trigger for cold acclimation? Plant Cell Physiol 44, 676-686

30. Godbolé, R., Michalke, W., Nick, P., Hertel, R. (2000) Cytoskeletal drugs and gravity-induced lateral auxin transport in rice coleoptiles. Plant Biology 2, 176-181

31. Nick, P., Heuing, A., Ehmann, B. (2000) Plant chaperonins: a role in microtubule-dependent wall-formation? Protoplasma 211, 234-244

25. Freudenreich, A., Nick, P. (1998) Microtubular organization in tobacco cells: heat-shock protein 90 can bind to tubulin in vitro. Bot. Acta 111, 1-7

26. Petrašek, J., Freudenreich, A., Heuing, A., Opatrný, Z., Nick, P. (1998) HSP90 is associated with microtubules in tobacco cells. Protoplasma 202, 161-174.

17. Nick,P., Lambert,A.-M., Vantard,M. (1995) A microtubule-associated protein in maize is expressed during phytochrome-induced cell elongation. Plant J. 8, 835-844