Multidrug resistance reversal activity of taxoids from Taxus cuspidata in KB-C2 and 2780AD cells

被引:18
作者
Kobayashi, J
Shigemori, H
Hosoyama, H
Chen, ZS
Akiyama, S
Naito, M
Tsuruo, T
机构
[1] Hokkaido Univ, Grad Sch Pharmaceut Sci, Kita Ku, Sapporo, Hokkaido 0600812, Japan
[2] Kagoshima Univ, Fac Med, Inst Canc Res, Kagoshima 8900075, Japan
[3] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan
来源
JAPANESE JOURNAL OF CANCER RESEARCH | 2000年 / 91卷 / 06期
关键词
multidrug resistance reversal activity; P-glycoprotein; taxoids; MDR modifiers;
D O I
10.1111/j.1349-7006.2000.tb00993.x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Some non-taxol-type taxoids having neither an oxetane ring at C-4 and C-5 nor an N-acylphenyl-isoserine group at C-13, such as taxuspine C, 2'-desacetoxyaustrospicatine, and 2-desocetoxytaxinine J, which were isolated from the Japanese yew Taxus cuspidata, increased cellular accumulation of vincristine (VCR) in multidrug-resistant 2780hD cells as potently as verapamil, and efficiently inhibited [H-3]azidopine photolabeling of P-glycoprotein (P-gp). Taxuspine C, 2'-desacetoxyaustrospicatine, and 2-desacetoxytaxnine J at 10 mu M completely reversed the resistance to colchicine. VCR, and taxol in RB-C2 cells, which overexpress P-gp, while taxinine and taxinine M shelved no effect. Taxuspine C, 2'-desacetoxyaustrospicatine, and 2-desacetoxytaxinine J may he candidate pharmaceuticals for reversing multidrug resistance (MDR) and also may be good modifiers of MDR in cancer chemotherapy.
引用
收藏
页码:638 / 642
页数:5
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