Effects of taxoids from Taxus cuspidata on microtubule depolymerization and vincristine accumulation in MDR cells
✍ Scribed by Jun'ichi Kobayashi; Hirokazu Hosoyama; Xiao-xia Wang; Hideyuki Shigemori; Yukiko Koiso; Shigeo Iwasaki; Takuma Sasaki; Mikihiko Naito; Takashi Tsuruo
- Publisher
- Elsevier Science
- Year
- 1997
- Tongue
- English
- Weight
- 410 KB
- Volume
- 7
- Category
- Article
- ISSN
- 0960-894X
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✦ Synopsis
Among new taxoids, taxuspines A -H and J -T (1 -19), and known taxoids 20 -56 containing taxol (56) and taxol-type compounds 37 -44 with an N-acylphenylisoserine group at C-13 and an oxetane ring at C-4 and C-5 isolated from stems and leaves of the Japanese yew Taxus cuspidata Sieb. et Zucc., nontaxol-type compounds 4 and 32 remarkably reduced CaC12-indaced depolemerization of microtubules. Furthermore, some non-taxol-type compounds 2, 3, 9, 24, 25, 27, and 28 increased cellular accumulation of vincristine in multidrug-resistant tumor cells as potent as verapamil, while taxol (36) and taxol-type compounds did not show such an activity. In addition, the non-taxol-type compounds enhancing vincristine accumulation inhibited competitively binding of azidopine to P-glycoprotein. These results suggest that some non-taxol-type taxoids may be useful for overcoming multidrug resistance in tumor cells.