P-GLYCOPROTEIN MEDIATES PROFOUND RESISTANCE TO BISANTRENE

Bisantrene, mitoxantrone, and anthracyclines are anthracene derivative s that interact with DNA and are used for the treatment of cancers. Th e mechanisms of resistance to bisantrene are unknown. Here we show tha t cells that overexpress low levels of P-glycoprotein or are transfect ed with human MDR1 have approximately 10-fold greater resistance to bi santrene compared to vinblastine, doxorubicin, or colchicine. Furtherm ore, bisantrene can be used to select for high-level P-glycoprotein-me diated multiple drug resistance in a human colon carcinoma eel line, L S 174T, and the drug blocks photoaffinity labeling of P-glycoprotein. The data suggest that bisantrene is an excellent substrate for P-glyco protein. These findings could influence subsequent clinical evaluation of bisantrene for the treatment of cancer.