Rosiglitazone-mediated stimulation of LA-12-induced apoptosis is accompanied by changes in colon cancer cell cycle progression

Rosiglitazone, a ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma), possess anticancer properties and has been shown to reduce growth and metastasis in some tumor types. PPAR gamma can affect the expression of many genes involved in regulation of cytokinetics and may also have a potential to be used as a sensitizer to the killing effects of some chemotherapeutic agents. LA-12 is a new platinumbased drug with increased intracellular penetration and better cytotoxic/cytostatic properties in cancer cells compared to conventionally used platinum chemotherapeutics. In order to further maximize its killing potential in colon cancer cells, LA-12 was combined with rosiglitazone, and molecular mechanisms involved in the increased toxicity of the drug combination were examined.

We showed that pretreatment of human colon cancer cells HCT116 with rosiglitazone resulted in p53-independent enhancement of LA-12-induced caspase-dependent apoptosis. These effects were accompanied with modulation of the cell cycle distribution, especially of S and G2/M phase, as documented by flow cytometry analysis of propidium iodidestained cells, and also reflected by changes of the level of relevant cell-cycle regulatory proteins. The results of a detailed analysis of apoptosis and cell cycle regulation following the combined action of rosiglitazone and LA-12 in colon cancer cells will be presented in our contribution.

This work was supported by the IGA of the Ministry of Health of the Czech Republic (NT/11201–5) and FNUSA-ICRC European Regional Development Fund No. CZ.1.05/1.1.00/02.0123, HistoPARK – CZ.1.07/2.3.00/20.0185