Open AccessNovel Mechanism of N‐Solanesyl‐N,N′‐bis(3,4‐dimethoxybenzyl)ethylenediamine in Potentiation of Antitumor Drug Action on Multidrug‐resistant and Sensitive Chinese Hamster Cells
Author(s) -
Tomida Akihiro,
Tatsuta Tohru,
Suzuki Hideo
Publication year - 1991
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1991.tb01755.x
Subject(s) - mechanism of action , ethylenediamine , verapamil , pharmacology , chemistry , hamster , biochemistry , biology , endocrinology , calcium , in vitro , inorganic chemistry , organic chemistry
The mechanism of the synthetic isopremoid N‐solanesyl‐N,N′‐bis(3,4‐dimethoxybenzyl)ethylenediantine (SDB‐ethylenediamine) in potentiating antitumor drug action against multidrug‐resistant cells was comparatively studied with other potentiators such as verapamil and cepharanthine. SDB‐ethylenediamine increased the accumulation of [ 3 H]daunorubicin (DNR) in Chinese hamster V79 (V79/S) and its multidrug‐resistant mutant (V79/ADM) cells. Even after SDB‐ethylenediamine was removed from the medium, its effect continued. But when verapamil was removed from the medium, its effect disappeared immediately. Unlike verapamil and cepharanthine, SDB‐ethylenediamine did not greatly inhibit the efflux of [ 3 H]DNR from V79/ADM, the binding of [ 3 H]vinblastine to membrane vesicles of V79/ADM, or the binding of [ 3 H]azidopine to P‐glycoprotein in the cytoplasmic membrane of V79/ADM. It did stimulate the influx of [ 3 H]DNR into the ATP‐depleted cells of V79/S and V79/ADM. Thus, SDB‐ethylenediamine uniquely potentiates antitumor drugs. The increased intracellular accumulation of antitumor drugs in the presence of SDB‐ethylenediamine is due not only to the inhibition of active efflux but also to the stimulation of the influx of antitumor drugs.