title: Potentiation of the cytostatic effect of bleomycin on L5178y mouse lymphoma cells by pepleomycin.
abstract: Bleomycin (BLM) and pepleomycin (PEP) are two chemically related glycopeptide antitumor antibiotics which differ in their terminal residues only. Studying the growth-inhibitory potencies of BLM (clinical mixture), BLM-A2, BLM-B2 and PEP in the L5178y mouse lymphoma cell culture system, it was elucidated that the slopes of the dose-response curves at the ED50 concentration (around 1 microgram/ml) were steeper for PEP than for BLM. This result together with cytotoxicity determinations revealed a cytostatic action of PEP within a closer concentration range than BLM. Both drugs inhibit cell proliferation during S- and G2-phase. Given in combination, BLM and PEP inhibit cell proliferation in a highly significant synergistic way (FIC indexes: 0.25-0.46). This in vitro result, which might be of therapeutic importance, is correlated with differences on the molecular level. Determinations of the ratio between the number of single- and double-strand breaks in the DNA (the target molecule of the drugs) revealed a considerably lower value for DNA from BLM-treated cells (1.9:1) than for DNA from PEP-treated cells (13:1).
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007399:Interphase / Q000187:drug effects; D007940:Leukemia L5178 / Q000473:pathology*; D007942:Leukemia, Experimental / Q000473:pathology*; D051379:Mice; D017663:Peplomycin
chemical_list: D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D001761:Bleomycin; D017663:Peplomycin