Comparative studies on biological activity of certain microtubule-interacting taxanes.
We have compared the nature of interaction of certain taxanes with microtubular protein, and the mechanism of action underlying cytotoxic activity. Taxanes induced tubulin assembly in vitro, but only taxanes bearing side chain were capable of inducing the formation of stable tubulin polymers. Electron microscopy detections showed that taxane-induced polymers are structurally similar to microtubules formed by paclitaxel, with differences in length. Otherwise, light microscopy views have shown that intracellular microtubule network is deeply reorganized by taxanes into short fibers, unlike paclitaxel-bundled microtubules. Taxanes inhibited the growth of various human tumor cell lines, but cell cycle analysis did not always indicate a block in the G2/M phase. These agents alter some apoptotic signal transduction pathways, probably by a mechanism distinct from microtubule interaction. Briefly, the effectiveness of taxanes is closely related to their chemical structure, and depends on their interaction with microtubular protein. By virtue of this mechanism, some of these taxanes may provide usefulness for therapeutic improvements.
Miglietta
Antonella
A
Department of Experimental Medicine and Oncology, University of Torino, Corso Raffaello 30, 10125 Torino, Italy. antonella.miglietta@unito.it
Bocca
Claudia
C
Gabriel
Ludovica
L
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000633:toxicity; D001943:Breast Neoplasms; D001952:Bridged-Ring Compounds / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms; D005260:Female; D016195:G2 Phase; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000187:drug effects*; D008938:Mitosis; D013329:Structure-Activity Relationship; D043823:Taxoids; D014404:Tubulin / Q000096:biosynthesis / Q000187:drug effects* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; D014404:Tubulin; C080625:taxane