Comparison of annamycin to adriamycin in cardiac and MDR tumor cell systems

Based on the response of a wide variety of tumors to the anthracycline, Adr iamycin, numerous studies have been initiated to find an even more effectiv e analog. In this pursuit two of the obstacles that have been necessary to overcome are a unique dose dependent Adriamycin-induced cardiotoxicity repo rted in patients treated with this chemotherapeutic agent as well as p-gp-m ediated multi drug resistance (MDR) which has been found in tumor cells exp osed to Adriamycin int vitro and in vivo as well as in human tumor samples. Using an in vitro cardiac cell system and MDR+ and MDR- Friend leukemia ce ll lines we find that a relatively new anthracycline, Annamycin, has reduce d cardiotoxic activity but is more effective in inhibiting the growth of MD R+ cells than Adriamycin. The reduced cardiotoxicity of Annamycin is approx imately 10 fold lower than Adriamycin whereas the increased efficacy agains t the MDR+ Friend leukemia tumor cell line is about 2 fold. The observation that Adriamycin preferentially accumulates in cardiac-muscle (CM) but not in cardiac non-muscle (NM) cells while Annamycin accumulates equally in bot h, may explain in part the reduced cardiotoxicity of Annamycin. Moreover, t he cytosolic accumulation of Annamycin vs the nuclear localization of Adria mycin suggests a different target site for each drug.