Multidrug Resistance Reversal Activity of Taxoids from Taxus cuspidate 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‐acylphenylisoserine 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 accumulation 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 10μM 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.