DNA topoisomerase I as a site of action for 10-hydroxycamptothecin in human promyelocytic leukemia cells.

We investigated the antiproliferative effect of 10-hydroxycamptothecin (HCPT), an alkaloid isolated from Camptotheca acuminata, on the human promyelocytic leukemia cell line, HL-60, and a 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA)-resistant mutant, HL-60/m-AMSA. Data suggest that the principle mechanisms for HCPT-induced cytotoxicity in HL-60 and HL-60/m-AMSA cells are inhibition of DNA topoisomerase I and production of protein-associated DNA strand breaks