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. 2001 Aug;92(8):886–895. doi: 10.1111/j.1349-7006.2001.tb01177.x

Reversing Effect of Agosterol A, a Spongean Sterol Acetate, on Multidrug Resistance in Human Carcinoma Cells

Shunji Aoki 1, Zhe‐Sheng Chen 2, Kimihiko Higasiyama 1, I Setiawan 1, Shin‐ichi Akiyama 2, Motomasa Kobayashi 1,✉
PMCID: PMC5926837  PMID: 11509122

Abstract

The effect of agosterol A, a novel polyhydroxylated sterol acetate isolated from a marine sponge, on P‐glycoprotein (P‐gp)‐mediated multidrug‐resistant cells (KB‐C2) and the multidrug resistance associated protein (MRPl)‐mediated multidrug‐resistant cells (KB‐CV60) was examined. Agosterol A reversed the resistance to colchicine in KB‐C2 cells and also the resistance to vincristine in KB‐CV60 cells at 3 to 10 μM concentration. Agosterol A at 3 μM increased the vincristine concentration in both KB‐C2 cells and KB‐CV60 cells to the level in parental KB‐3‐1 cells. Agosterol A also decreased the efflux of vincristine from both KB‐C2 cells and KB‐CV60 cells to the level seen in KB‐3‐1 cells. Agosterol A inhibited the [3H]azidopine‐photolabeling of P‐gp and also inhibited the uptake of [3H]S‐(2,4‐dinitrophenyl)glutathione (DNP‐SG) in inside‐out membrane vesicles prepared from KB‐CV60 cells. We conclude that agosterol A directly inhibited drug efflux through P‐gp and/or MRP1.

Keywords: Agosterol A, Multidrug resistance tumor, P‐Glycoprotein, Multidrug resistance associated protein, Glutathione

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