The Role of Copper in Development of Drug Resistance in Murine Carcinoma

Abstract

Multidrug resistance (MDR) is a major obstacle to successful application of cancer chemotherapy and also a basic problem in cancer biology. Studies on the molecular basis of MDR have revealed that a number of proteins over express in multidrug resistant cells viz., multidrug resistant MDR1 gene product P-glycoprotein, the multidrug resistance-associated protein (MRP) and enzymes associated with the glutathione (GSH) metabolism. Decreased expression or altered activity of topoisomerase II has also been implicated in MDR. In the present investigation a number of changes in phase II detoxification parameters have been noticed in drug resistant cells but the novel aspect of the present report is the observation that the metal copper is involved in drug resistance. Although copper plays important roles in many human and other biological systems and even in the treatment of cancer but the relation of Cu and drug resistance has not so far been studied in detailed. The present report describes the novel findings that the level of copper increases with the development of drug resistance in Ehrlich ascites carcinoma and in Lewis lung carcinoma cells and also in serum of mice bearing drug resistant cancer cells compared to mice bearing drug sensitive cells; the work indicates the important aspect of treating drug resistant cancer patients by lowering Cu level in the cancerous cells and serum prior to treatment.