Planta Med 1995; 61(5): 409-413
DOI: 10.1055/s-2006-958126
Paper

© Georg Thieme Verlag Stuttgart · New York

Reversal of Daunomycin and Vinblastine Resistance in Multidrug-Resistant P388 Leukemia in vitro through Enhanced Cytotoxicity by Triterpenoids

Hideo Hasegawa1 , Jong-Hwan Sung1 , Satoshi Matsumiya1 , Masamori Uchiyama1 , Yoshio Inouye2 , Ryoji Kasai2 , Kazuo Yamasaki2
  • 1Itto Institute of Life Science Research, Happy World Inc., 3-13-8, Shiraitodai, Fuchu-shi, Tokyo, 183, Japan
  • 2Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734, Japan
Further Information

Publication History

1994

1995

Publication Date:
04 January 2007 (online)

Abstract

Examined in vitro were the effects of some triterpenoids from Panax (Araliaceae) and Glycyrrhiza (Leguminosae) spp. on the sensitivity to daunomycin (DAU) and vinblastine (VBL) of adriamycin (ADM)-resistant P388 leukemia cells (P388/ADM), which were resistant to multiple anticancer drugs. Quasipanaxatriol, 20(S)-protopanaxatriol, ginsenoside Rh2, and compound K greatly enhanced the cytotoxicity of the anti-cancer drugs in P388/ADM cells. The extent of enhancement was different among the triterpene compounds; the 4- to 46-fold increase in DAU cytotoxicity was observed in P388/ADM cells in the presence of non-toxic or marginally toxic concentrations of individual compounds, while those for VBL were in the ratios of 2- to 37-fold. The maximum increase in cytotoxicity was observed with 50 µM quasipanaxatriol; the resistance indices defined to be the ratios of the IC50 values for P388/ADM and P388 parental cells decreased from 79 to 1.7 and from 180 to 4.9 in the cases of DAU and VBL, respectively. The reversal of DAU resistance in P388/ADM by quasipanaxatriol could be explained by the effective accumulation of the drugs mediated by the DAU-efflux blockage.