Enhancing effect of reserpine upon the cytotoxicity of ACNU on ACNU resistant glioma cells.

Abstract

Reserpine has enhanced the cytotoxicity of 1 (4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) in both ACNU-resistant sublines of C6 and 9L glioma cells (C6/ACNU, 9L/ACNU) and could completely overcome ACNU resistance in vitro. When reserpine was added to the culture in the concentration of 10μpM, the concentrations of drug required for 50% inhibition of cell growth of ACNU for C6/ACNU and 9L/ACNU cells decreased to the level of those for C6 and 9L cells, respectively. Intracellular uptake and retention of ACNU in both ACNU-resistant cells increased when 20μM reserpine was added to the culture. It is suggested that the enhanced effect of cytotoxicity of ACNU in ACNU-resistant glioma cells is presumably due to the increase of intracellular concentration of ACNU through the inhibition of the efflux of intracellular ACNU from resistant cells.