Heterocyclic complexes of ruthenium(III) induce apoptosis in colorectal carcinoma cells
- Author(s)
- S Kapitza, Martina Pongratz, Michael Jakupec, Petra Heffeter, Walter Berger, L Lackinger, Bernhard Keppler, Brigitte Marian
- Abstract
Purpose: The ruthenium complex salt indazolium trans- [tetrachlorobisindazole-ruthenate(III)] (KP1019) and the analogous sodium salt KP1339 are effective tumor-inhibiting drugs in experimental therapy of autochthonous colorectal carcinomas in rats. This paper examines the cell biological mechanisms underlying their antineoplastic effects. Methods: Colorectal tumor cell lines were used to analyze uptake of the ruthenium(III) complexes into the cells and the mechanism as well as the efficacy of their cytotoxic effects. Results: KP1019 and KP1339 are efficiently taken up into the cells: 100 œM ruthenium(III) complex in the growth medium led to the uptake of 120-160 ng ruthenium per 106 cells within 30 min. Uptake of KP418 was tenfold lower correlating with its lower cytotoxic efficiency. KP1019 and KP1339 induced apoptosis in SW480 and HT29 cells predominantly by the intrinsic mitochondrial pathway as indicated by loss of mitochondrial membrane potential. Correspondingly sensitivity of the cells paralleled expression of bcl 2 while it was only slightly affected by mutations in Ki-ras. Conclusions: Our data demonstrate that trans-[tetrachlorobisindazole- ruthenate(III)] complex salts are promising candidate drugs in the second-line treatment of colorectal cancers resistant to other cytostatic drugs and has been introduced into phase I clinical trials. Œ Springer-Verlag 2004.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Medizinische Universität Wien
- Journal
- Journal of Cancer Research and Clinical Oncology
- Volume
- 131
- Pages
- 101-110
- No. of pages
- 10
- ISSN
- 0171-5216
- Publication date
- 2005
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 301904 Cancer research
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/8e228575-2e91-4252-b950-e69835225473