title: Cytotoxicity of monensin, narasin and salinomycin and their interaction with silybin in HepG2, LMH and L6 cell cultures.
abstract: The cytotoxic effect of monensin, narasin and salinomycin followed by their co-action with silybin in the cell line cultures of human hepatoma (HepG2), chicken hepatoma (LMH) or rat myoblasts (L6) have been investigated. The effective concentration of the studied ionophoric polyethers has been assessed within two biochemical endpoints: mitochondrial activity (MTT assay) and membrane integrity (LDH assay) after 24h incubation of each compound and farther, the cytotoxicity influenced in course of their interaction with silybin was determined. The most affected endpoints were found for inhibition of mitochondrial activity of the hepatoma cell lines and their viability depended on concentration of the ionophoric polyether, as well as on the cell line tested. The rat myoblasts were more sensitive target for cellular membrane damage when compared to inhibition of mitochondrial activity. An interaction between the ionophoric polyethers and silybin resulted a considerable cytotoxicity decrease within all studied cell lines; the combination index (CI) showed differences of interaction mode and dependence on cell culture, concentration of silybin, as well as the assay used. The obtained results are of interest in respect to recent findings on applicability of salinomycin and monensin for human therapy.
authors.affiliation: Department of Pharmacology and Toxicology, National Veterinary Research Institute, Partyzantow 57, 24-100 Pulawy, Poland. Electronic address: wojciech.cybulski@piwet.pulawy.pl.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Cybulski
authors.affiliation: Department of Pharmacology and Toxicology, National Veterinary Research Institute, Partyzantow 57, 24-100 Pulawy, Poland. Electronic address: lidia.radko@piwet.pulawy.pl.
authors.forename: Lidia
authors.initials: L
authors.lastname: Radko
authors.affiliation: Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, Poland; Department of Medical Biology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin, Poland. Electronic address: rzeskiw@hektor.umcs.lublin.pl.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Rzeski
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D004347:Drug Interactions; D056945:Hep G2 Cells; D006801:Humans; D008985:Monensin / Q000633:toxicity*; D032446:Myoblasts / Q000187:drug effects; D011714:Pyrans / Q000633:toxicity*; D051381:Rats; D000077385:Silybin; D012838:Silymarin / Q000633:toxicity*; D000095662:Polyether Polyketides
chemical_list: D008985:Monensin; D011714:Pyrans; D000077385:Silybin; D012838:Silymarin; C010327:salinomycin; D000095662:Polyether Polyketides; C013612:narasin
keywords: Cytoprotecion; HepG2 cells; Ionophoric polyethers; L6 cells; LMH cells; Silybin