title: Synergism of the polyamine analogue, N1,N11-bisethylnorspermine with cis-diaminedichloroplatinum (II) against murine neoplastic cell lines in vitro and in vivo.
abstract: The activities of naturally occurring polyamines are exploited to enhance the antitumor activity of cisplatin. The polyamine analogue, N1,N11-bis-ethylnorspermine (BE-3-3-3) is used at subtherapeutic levels in L1210 leukemia suspension cultures and plating efficiency assays of B16 F1 melanoma cells to increase the cytotoxic effect of cisplatin seven- and ten-fold, respectively. Similar experiments in mice reveal additive effects for DBA/2J mice bearing L1210 and synergistic effects in C57/B6 mice bearing B16 F1 tumor after optimizing combination ratios. In the latter model, at a BE-3-3-3/cisplatin molar ratio of 250:1, an increased lifespan (ILS) of 56% is recorded during a 9-day dosing schedule, whereas BE-3-3-3 at the same dose caused a 21% ILS, and cisplatin only exhibited a 7% ILS. Possible reasons for differences between in vitro and in vivo activity are discussed.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville 32610, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Hawthorne
authors.forename: J K
authors.initials: JK
authors.lastname: Austin
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D004198:Disease Susceptibility; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D013096:Spermine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: C059685:N(1),N(11)-diethylnorspermine; D013096:Spermine; D002945:Cisplatin