DNA crosslinking by 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin in HT-29 human colon carcinoma cells in vitro.
The Adriamycin analog, 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin, is 100- to 1000-fold more active than Adriamycin as an antitumor agent in vivo and in vitro. The interaction of 3'-(3-cyano-4-morpholinyl)-3'deaminoadriamycin and Adriamycin with DNA has been studied in HT-29 human colon carcinoma cells in vitro. The Adriamycin analog produced significant DNA-DNA crosslinking at a drug concentration range that resulted in from 1 to 4 logs of cell kill, but did not produce any DNA-protein crosslinks. Equitoxic concentrations of Adriamycin produced no significant levels of DNA-DNA crosslinks. The formation of DNA-DNA crosslinks by the Adriamycin derivative is an additional mechanism of action that may account for the high potency of this agent.
D002460:Cell Line; D003110:Colonic Neoplasms / Q000378:metabolism*; D003432:Cross-Linking Reagents; D004247:DNA / Q000378:metabolism*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D011506:Proteins / Q000378:metabolism
D003432:Cross-Linking Reagents; D011506:Proteins; D004317:Doxorubicin; C038555:3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin; D004247:DNA