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-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.