Effect of reactivity on cellular accumulation and cytotoxicity of oxaliplatin analogues
- Author(s)
- Irina Buss, Ganna V. Kalayda, Andreas Lindauer, Michael Reithofer, Mathea Sophia Galanski, Bernhard Keppler, Ulrich Jaehde
- Abstract
The purpose of this study was to systematically investigate the relationships between reactivity, cellular accumulation, and cytotoxicity of a panel of oxaliplatin analogues with different leaving groups in human carcinoma cells. The reactivity of the complexes towards the nucleotides 2'-deoxyguanosine 5'-monophosphate and 2'-deoxyadenosine 5'-monophosphate was studied using capillary electrophoresis. Cellular accumulation and cytotoxicity were measured in an oxaliplatin-sensitive and oxaliplatin-resistant ileocecal colorectal adenocarcinoma cell line pair (HCT-8/HCT-8ox). Platinum concentrations were determined by flameless atomic absorption spectrometry. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to assess cytotoxicity. Early cellular platinum accumulation was predominantly affected by lipophilicity. A relationship between reactivity and cellular accumulation was observed for three of four platinum complexes investigated, whereas the most lipophilic oxaliplatin analogue was an exception. Increased reactivity and reduced lipophilicity were associated with high cytotoxic activity. Resistance was influenced by lipophilicity but not by reactivity. The observed relationships may help in the design of analogues with high antitumoral activity in oxaliplatin-sensitive as well as oxaliplatin-resistant cells.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Rheinische Friedrich-Wilhelms-Universität Bonn
- Journal
- Journal of Biological Inorganic Chemistry
- Volume
- 17
- Pages
- 699-708
- No. of pages
- 10
- ISSN
- 0949-8257
- DOI
- https://doi.org/10.1007/s00775-012-0889-9
- Publication date
- 2012
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 106002 Biochemistry
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/5bd0b373-f961-4e95-afa4-c1d0dc015c3b