title: The influence of electroporation on cytotoxicity of anticancer ruthenium(III) complex KP1339 in vitro and in vivo.
abstract: In our study, the ruthenium-based anticancer agent KP1339 was tested in combination with electroporation for its cytotoxic effect on CHO and SA-1 cell lines in vitro and on SA-1 murine tumour model in vivo. Cells were treated with different doses of KP1339 for 15 or 60 min with or without electroporation in vitro. Cell viability was measured with the MTS assay. In vivo, mice bearing SA-1 tumours were treated with different doses of KP1339 with or without electroporation. Tumour growth was measured at various time points after treatment. Intratumoural ruthenium content was analysed as a measure of KP1339 accumulation to correlate it with antitumour effectiveness. Our results show that electroporation does not potentiate the cytotoxicity of KP1339 in vitro, but significantly potentiates antitumour effectiveness in vivo. Electroporation enhanced ruthenium uptake immediately after treatment, consequently causing persistently higher intratumoural ruthenium content throughout the whole observation period (48 h). In addition, ruthenium content rose continuously in electroporated and intact tumours throughout the whole observation period. The observed antitumour effectiveness is the result of both the direct cytotoxicity of KP1339 and an antivascular effect of electroporation.
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
authors.forename: Rosana
authors.initials: R
authors.lastname: Hudej
authors.forename: Iztok
authors.initials: I
authors.lastname: Turel
authors.forename: Masa
authors.initials: M
authors.lastname: Kanduser
authors.forename: Janez
authors.initials: J
authors.lastname: Scancar
authors.forename: Simona
authors.initials: S
authors.lastname: Kranjc
authors.forename: Gregor
authors.initials: G
authors.lastname: Sersa
authors.forename: Damijan
authors.initials: D
authors.lastname: Miklavcic
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jakupec
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
authors.forename: Maja
authors.initials: M
authors.lastname: Cemazar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D018274:Electroporation; D051379:Mice; D009942:Organometallic Compounds / Q000494:pharmacology*; D012513:Sarcoma, Experimental / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; C551585:KP 1339; D009942:Organometallic Compounds