A fluorescent oxaliplatin derivative for investigation of oxaliplatin resistance using imaging techniques
- Author(s)
- Ganna V. Kalayda, Maximilian Kullmann, Mathea Sophia Galanski, Sabrina Gollos
- Abstract
Oxaliplatin is the backbone of chemotherapy for advanced colorectal cancer and undergoes clinical trials for treatment of other tumour entities. However, acquired resistance is a major hurdle. Confocal microscopy is a useful tool to get an insight into the mechanisms of resistance but it requires fluorescent compounds. This work describes the synthesis of the novel oxaliplatin derivative (CFDA-oxPt) featuring 5(6)-carboxyfluorescein diacetate and evaluation of its applicability for the investigation of oxaliplatin resistance using imaging techniques. CFDA-oxPt was somewhat less cytotoxic than oxaliplatin in sensitive colorectal cancer cells, with EC
50 values of 26 and 5.8 µM, respectively. Nevertheless, the potency of the novel complex was significantly decreased to the EC
50 of 711.2 µM in oxaliplatin-resistant cells, as was the case for oxaliplatin (EC
50 = 81 µM). After incubation, both nuclear and cytosolic localisation was observed. Over time CFDA-oxPt concentrated near the cell membrane and in the vesicular structures, in contrast to the platinum-free label, which was rapidly excreted. These findings suggest that CFDA-oxPt can be used to study oxaliplatin resistance and open the route to new fluorophore-tethered oxaliplatin derivatives.
- Organisation(s)
- NMR Centre, Department of Inorganic Chemistry
- External organisation(s)
- Rheinische Friedrich-Wilhelms-Universität Bonn
- Journal
- Journal of Biological Inorganic Chemistry
- Volume
- 22
- Pages
- 1295-1304
- No. of pages
- 10
- ISSN
- 0949-8257
- DOI
- https://doi.org/10.1007/s00775-017-1502-z
- Publication date
- 12-2017
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 104004 Chemical biology
- Keywords
- ASJC Scopus subject areas
- Biochemistry, Inorganic Chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/608ad28e-660b-4404-8528-8e498dcd0dde