LA-12 Overcomes Confluence-dependent Resistance of HT-29 Colon Cancer Cells to Pt (II) Compounds

Časopis: ANTICANCER RESEARCH 30, 1183-1188
Autoři: Svihalkova-Sindlerova, L., Foltinova, V., Vaculova, A., Horvath, V., Soucek, K., Sova, P., Hofmanova, J., Kozubik, A.
Rok: 2010


Background: LA-12 is a new platinum (IV) drug with promising cytotoxic effects in a wide range of cancer cell lines. Its confluence-dependent effects were compared with cisplatin (CDDP) and oxaliplatin (L-OHP) in HT-29 cells. Materials and Methods: Cytotoxicity was determined by MTT test, eosin exclusion assay, and cell number quantification. The cell cycle was analysed using propidium iodide DNA staining (flow cytometry), apoptosis by phosphatidylserine externalisation (annexin-V assay), mitochondrial membrane potential by flow cytometry, nuclear morphology by means of fluorescence microscopy, and PARP cleavage by Western blotting. Results: While L-OHP and CDDP were practically inactive in the subconfluent cell population, LA-12 showed a similar toxicity in both subconfluent and growing populations. All compounds induced apoptosis, although with different potentials. Conclusion: LA-12 was able to overcome confluence-dependent resistance of HT-29 cells observed for other platinum compounds, which may have potential therapeutic use in slowly growing tumours.