Enhanced effect of reserpine upon growth-inhibitory action of ACNU on ACNU-resistant C6 glioma.

Reserpine was found to enhance the cytotoxicity of ACNU on ACNU-resistant C6 glioma (C6/ACNU) cells in vitro. When reserpine was added along with ACNU to the C6/ACNU cells in vitro. When reserpine was added along with ACNU to the C6/ACNU culture in vitro at a concentration of 10 microM, the IC50 of ACNU for C6/ACNU cells decreased to the level of that for C6 cells and ACNU resistance was completely overcome in vitro. Furthermore, intracellular uptake of ACNU increased in both sensitive (C6) and resistant (C6/ACNU) glioma cells when 20 microM reserpine was added to the culture medium. Reserpine (20 microM) enhanced the cellular level of ACNU in C6 cells 1.5-fold and enhanced the level of ACNU in C6/ACNU cells 4-fold. The amount of ACNU incorporated into C6/ACNU cells reached the same level as that incorporated into C6 cells. The enhanced cytotoxicity of ACNU in vitro could be explained by the effective intracellular accumulation of ACNU resulting from the increase of intracellular uptake of ACNU in C6/ACNU cells by reserpine.