The influence of electroporation on cytotoxicity of anticancer ruthenium(III) complex KP1339 in vitro and in vivo

Author(s)
Rosana Hudej, Iztok Turel, Masa Kanduser, Janez Scancar, Simona Kranjc, Gregor Sersa, Damijan Miklavcic, Michael Jakupec, Bernhard Keppler, Maja Cemazar
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.

Organisation(s)
Department of Inorganic Chemistry
External organisation(s)
University of Ljubljana, Jožef Stefan Institute (IJS)
Journal
Anticancer Research: International journal of cancer research and treatment
Volume
30
Pages
2055-2063
No. of pages
9
ISSN
0250-7005
Publication date
2010
Peer reviewed
Yes
Austrian Fields of Science 2012
104003 Inorganic chemistry, 301305 Medical chemistry
Portal url
https://ucrisportal.univie.ac.at/en/publications/81607ce0-2833-4258-b600-cf465dbebcda