Multidrug resistance reversal activity of taxoids from Taxus cuspidata in KB-C2 and 2780AD cells.
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-desacetoxytaxinine J, which were isolated from the Japanese yew Taxus cuspidata, increased cellular accu-mulation of vincristine (VCR) in multidrug-resistant 2780AD cells as potently as verapamil, and efficiently inhibited [(3)H]azidopine photolabeling of P-glycoprotein (P-gp). Taxuspine C, 2'-desacetoxyaustrospicatine, and 2-desacetoxytaxinine J at 10 microM completely reversed the resistance to colchicine, VCR, and taxol in KB-C2 cells, which overexpress P-gp, while taxinine and taxinine M showed no effect. Taxuspine C, 2'-desacetoxyaustrospicatine, and 2-desacetoxytaxinine J may be candidate pharmaceuticals for reversing multidrug resistance (MDR) and also may be good modifiers of MDR in cancer chemotherapy.
Kobayashi
J
J
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan. jkobay@pharm.hokudai.ac.jp.
Shigemori
H
H
Hosoyama
H
H
Chen
Z
Z
Akiyama
S
S
Naito
M
M
Tsuruo
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D003078:Colchicine / Q000494:pharmacology; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020128:Inhibitory Concentration 50; D007624:KB Cells; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology; D010946:Plants, Medicinal; D013329:Structure-Activity Relationship; D020946:Taxus; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000493:pharmacokinetics / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D017239:Paclitaxel; D003078:Colchicine