ENHANCED IN-VITRO CYTOTOXICITY OF IDARUBICIN COMPARED TO EPIRUBICIN AND DOXORUBICIN IN RAT PROSTATE CARCINOMA-CELLS

Objective: We evaluated the cytotoxic activity of the three anthracycl ines, doxorubicin, epirubicin and idarubicin, in different sublines of the Dunning rat prostate carcinoma as well as in multidrug-resistant KB cells, expressing a high amount of the human multidrug resistance g ene product, P glycoprotein. Methods: The effectiveness of the three a nthracyclines was tested in vitro in the Dunning rat prostate carcinom a sublines G, AT.1, AT.3.1, MatLu, and MatLyLu, as well as in multidru g-resistant KB cells, using an MTT assay. Results: All drugs were clea rly more effective in the androgen-sensitive Dunning rat prostate carc inoma subline G than in the androgen-independent growing sublines AT.1 , AT.3.1, MatLu, and MatLyLu. Idarubicin was much more effective than doxorubicin or epirubicin. To further elucidate the mechanism of actio n of idarubicin as compared with doxorubicin and epirubicin, we tested the cytotoxicity of these anthracyclines in highly multidrug-resistan t KB-V1 cells, which express high amounts of P glycoprotein, as well a s in the drug-sensitive parental KB-3-1 cells. KB-V1 cells proved to b e highly resistant to doxorubicin and epirubicin with IC50 values of 2 ,300 and 1,000 ng/ml, respectively. Idarubicin, however, was about 57. 5-fold and 25-fold more active, respectively, suggesting, that it is a ble to overcome P-glycoprotein-mediated multidrug resistance. Conclusi on: The strong in vitro effectiveness of idarubicin in androgen-insens itive prostate carcinoma cells suggests that this drug might be useful in the treatment of hormone-refractory prostate carcinoma.