title: Murine breast carcinoma 4T1 cells are more sensitive to atranorin than normal epithelial NMuMG cells in vitro: Anticancer and hepatoprotective effects of atranorin in vivo.
abstract: The aim of this study was to evaluate the anticancer effect of atranorin (ATR) on murine 4T1 breast carcinoma cells and compare its sensitivity with normal mammary epithelial NMuMG cells in vitro. Anti-tumor and hepatoprotective activity of ATR-therapy was examined on mouse model of 4T1-induced cancer disease. ATR significantly reduced clonogenic ability of carcinoma 4T1 cells at the concentration of 75 μM, but clonogenicity of normal NMuMG cells was not affected by any of ATR concentrations tested. Moreover, flow cytometric and BrdU incorporation analysis did not confirm the inhibited entry into S-phase of the cell cyle after ATR incubation, and on the contrary, it induced apoptosis associated with the activation of caspase-3 and PARP cleavage in 4T1 cells. Although ATR did not cause any significant changes in Bcl-xL protein expression in NMuMG cells, an apparent depletion of Bcl-xL protein in 4T1 cells after 48 h ATR therapy was confirmed. Based on this result as well as the result of the total cell number decline, we can conclude that 4T1 cells are more sensitive to ATR therapy than NMuMG cells. ATR administration resulted in significantly longer survival time of BALB/c mice inoculated with 4T1 cells, what was associated with reduced tumor size and the higher numbers of apoptotic 4T1 cells. No differences were recorded in the number of BrdU-positive tumor cells between ATR-treated group and controls. Results indicate that ATR has rather proapoptotic than antiproliferative effect on 4T1 cells in vitro and in vivo and normal NMuMG cells are less sensitive to ATR. Furthermore, our studies revealed protective effect of ATR against oxidative stress in the livers of the tumor-bearing mice.
authors.affiliation: Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University in Košice, 040 01 Košice, Slovak Republic. Electronic address: peter.solar@upjs.sk.
authors.forename: Peter
authors.initials: P
authors.lastname: Solár
authors.affiliation: Parasitological Institute of the Slovak Academy of Sciences, 040 01 Košice, Slovak Republic.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Hrčková
authors.affiliation: Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University in Košice, 040 01 Košice, Slovak Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Koptašíková
authors.affiliation: Parasitological Institute of the Slovak Academy of Sciences, 040 01 Košice, Slovak Republic.
authors.forename: Samuel
authors.initials: S
authors.lastname: Velebný
authors.affiliation: Institute of Pharmacology, Faculty of Medicine, P.J. Šafárik University in Košice, 040 01 Košice, Slovak Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Solárová
authors.affiliation: Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University in Košice, 040 01 Košice, Slovak Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Bačkor
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001940:Breast / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D062385:Hydroxybenzoates / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D062385:Hydroxybenzoates; C026304:atranorin; D053148:Caspase 3
keywords: 4T1 breast cancer; Atranorin; BALB/c mouse; Lichen; Lipid peroxidation; NMuMG cells