LA-12 overcomes confluence-dependent resistance of HT-29 colon cancer cells to Pt (II) compounds.

Lenka Svihálková-Sindlerová, Vendula Foltinová, Alena Vaculová, Viktor Horváth, Karel Soucek, Petr Sova, Jirina Hofmanová, Alois Kozubík

Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 612 65 Brno, Czech Republic.

Anticancer research 2010 Apr

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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. 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. 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. 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.

Citation

Lenka Svihálková-Sindlerová, Vendula Foltinová, Alena Vaculová, Viktor Horváth, Karel Soucek, Petr Sova, Jirina Hofmanová, Alois Kozubík. LA-12 overcomes confluence-dependent resistance of HT-29 colon cancer cells to Pt (II) compounds. Anticancer research. 2010 Apr;30(4):1183-8