抄録
In order to investigate the exact mechanism of the antitumor activity of two representative flavonoids, quercetin and genistein, an immunohistochemical 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 concentration of 20μM. Similar morphological changes, cytoplasmic distention and rounding, were observed with vinblastine administration at a lower concentration, but cells treated with genistein were not much different from the control cells. On immunohistochemical observation of α-tubulin by a CLSM (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, α-tubulin microtubules were distributed in a disorganized manner showing “criss-cross” patterns and focal aggregations. This feature was quite similar to that of vinblastinetreated cells. This immunohistochemically demonstrated microtubule disassembly was substantiated by semi quantitation of microtubule disassembly done by western blot analysis of α-tubulin which showed a distinct reduction of the polymerized microtubules in the quercetin- and vinblastine-treated cells. Furthermore, in vitro microtubule assembly tests proved that quercetin has definite inhibitory action, though it was with a lower potency than vinblastine, for the microtubule assembly through its direct interaction with tubulin molecules.
