Quercetin, a flavonol, promotes disassembly of microtubules in prostate cancer cells: Possible mechanism of its antitumor activity

In order to investigate the exact mechanism of the antitumor activity of tw o representative flavonoids, quercetin and genistein, an immunohistochemica l study and the supportive biochemical analyses on microtubule assembly and disassembly were performed using hormone refractory human prostate cancer cells in culture (PC3). Quercetin administration caused distinct morphological changes at a concent ration of 20 mu M. Similar morphological changes, cytoplasmic distention an d rounding, were observed with vinblastine administration at a lower concen tration, but cells treated with genistein were not much different from the control cells. On immunohistochemical observation of alpha-tubulin by a CLS M (Confocal Laser Scanning Microscopy), microtubules were exhibited as fine linear structures running regularly along the long axes of the control and genistein-treated cells. In quercetin-treated cells, however, alpha-tubuli n microtubules were distributed in a disorganized manner showing "criss-cro ss" patterns and focal aggregations. This feature was quite similar to that of vinblastine-treated cells. This immunohistochemically demonstrated micr otubule disassembly was substantiated by semi quantitation of microtubule d isassembly done by western blot analysis of alpha-tubulin which showed a di stinct reduction of the polymerized microtubules in the quercetin- and vinb lastine-treated cells. Furthermore, in vitro microtubule assembly tests pro ved that quercetin has definite inhibitory action, though it was with a low er potency than vinblastine, for the microtubule assembly through its direc t interaction with tubulin molecules.