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

Hideo Hasegawa; Jong-Hwan Sung; Satoshi Matsumiya; Masamori Uchiyama; Yoshio Inouye; Ryoji Kasai; Kazuo Yamasaki

doi:10.1055/s-2006-958126

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

Paper

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

Abstract

PDF Download

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.

Key words

Drug resistance - adriamycin (ADM)-resistant P388 leukemia (P388/ADM) - Panax - Araliaceae - Glycyrrhiza - Leguminosae - triterpenoid - daunomycin (DAU) - vinblastine (VBL)

PDF (429 kb)