Study of the mechanisms for cytotoxic effects of adrenocorticolytic and antimitotic drugs in human adrenocorticocytes

Abstract

Antimitotic agents are nowadays widely used as antitumor therapeutic agents. However, their use has some limitations, since the latter is a substrate of P-glycoprotein, which determines the resistance of cells to anticancer drugs. The aim is to investigate the effect of a selective P-glycoprotein PGP4008 inhibitor on realization the adrenocorticolytic compound ortho, para’-dichlorodiphenyldichloroethane (o, p’-DDD) actions and the antimitotic compounds of colchicine and cytochalasin B in human adrenocorticocytes. Material and methods. In vitro studies were performed on dispersed cells derived from non-tumor tissue of the human adrenal cortex. A solution of o, p’-DDD (final concentration of 10 and 50 μmol/l), colchicine (10 μmol/l) and cytochalasin B (10 μmol/l) were added to the incubation medium. A selective P-glycoprotein PGP4008 inhibitor was introduced into the incubation medium at a final concentration of 50 μmol/l. The incubation lasted for 18 h at 37 °C. The cytotoxic effects of the test compounds were evaluated by calculating the number of dead cells stained with 0.4% trypan blue in the Goryaev’s camera. Results. Preincubation of adrenocortical cells with o, p’-DDD, colchicine and cytochalasin B increases the percentage of dead cells. Addition of the PGP4008 to nutrient medium enhanced the cytotoxic effect of the test compounds. Conclusion. Studies have shown that the use of o, p’-DDD, colchicine and cytochalasin B with the PGP4008 P-glycoprotein inhibitor is promising for further preclinical study.