DILTIAZEM POTENTIATION OF DOXORUBICIN CYTOTOXICITY AND CELLULAR UPTAKE IN EHRLICH ASCITES-CARCINOMA CELLS

The calcium channel blocker diltiazem, which possesses coronary vasodi lator activity, greatly enhanced the cytotoxicity of doxorubicin in Eh rlich ascites carcinoma cells. 20% of the doxorubicin-treated tumor-be aring animals (2 mg/kg, every other day, three doses) survived, with a mean survival time of 35 days. However, pretreatment with diltiazem i ncreased survival to 70% with a mean survival time of 43 days. Diltiaz em treatment increased the intracellular level of doxorubicin, and the re was a good correlation between the high cellular level of doxorubic in and its cytotoxic activity. In tumor-bearing animals pretreated wit h diltiazem, doxorubicin showed a pronounced inhibitory effect on cell ular DNA, RNA content and acid phosphatase activity of tumor cells. In addition, there was a marked increase in cellular cholesterol and lip id contents. This study may suggest the benefit of using diltiazem to potentiate the cytotoxic effect of doxorubicin, allowing its dose and consequently the serious side effects to be reduced.