ed-110 and Leukemia-P388

ED-110 is a new semisynthetic antitumor agent derived from a novel indolocarbazole antibiotic, BE-13793C, produced by an actinomycete. ED-110 induced topoisomerase I-mediated DNA cleavage in vitro as strongly as camptothecin, whereas topoisomerase II-mediated DNA cleavage was not induced by this agent. Exposure of P388 cells to ED-110 caused a typical topoisomerase toxicity, i.e.: formation of cleavable complexes; inhibition of nucleotide synthesis rather than protein synthesis; and cell cycle arrest in G2. ED-110 inhibited the growth of P388 cells, with a 50% growth-inhibitory concentration of 44 nM. ED-110 is distinguished from camptothecin by its very different structure and its ability to intercalate into double-stranded DNA. These results suggest that ED-110 has potential as a novel antitumor agent targeting topoisomerase I.

Topics: Animals; Antineoplastic Agents; Binding, Competitive; Carbazoles; Cattle; Cell Division; DNA Damage; DNA Topoisomerases, Type I; DNA Topoisomerases, Type II; DNA, Neoplasm; DNA, Superhelical; Enzyme Induction; Flow Cytometry; Glucosides; Leukemia P388; Mice; Neoplasm Proteins; RNA, Neoplasm; Tumor Cells, Cultured

Topics: Animals; Antibiotics, Antineoplastic; Carbazoles; Female; Glucosides; Indoles; Leukemia P388; Mice; Molecular Structure; Pyrroles