Question:

Serum and glucocorticoid inducible kinase SGK1 was originally cloned from mammary tumor cells, is highly expressed in some tumors and confers survival to several tumor cells. Genetic SGK1 knockout decreased the number of colonic tumors following chemical cancerogenesis. Recently, a highly selective SGK1 inhibitor (EMD638683) has been developed. The present study explored whether EMD638683 affects survival of colon carcinoma cells in vitro and impacts on colonic tumors in vivo.

Methods:

Colon carcinoma (Caco-2) cells were treated with EMD638683 and/or radiation (3 Gray) and cell volume estimated from forward scatter, phosphatidylserine exposure from annexin-V binding, mitochondrial potential from DiOC₆ fluorescence, caspase 3 activity from CaspGlow Fluorescein staining and late apoptosis from APOPercentage Apoptosis Assay. Moreover, wild type mice were subjected to chemical cancerogenesis (intraperitoneal injection of 20 mg/kg 1,2-dimethylhydrazine followed by three cycles of 30 g/L synthetic dextran sulfate sodium in drinking water for 7 days).

Results:

EMD638683 treatment significantly augmented the radiation-induced decrease of forward scatter, increase of phosphatidylserine exposure, decrease of mitochondrial potential, increase of caspase 3 activity and increase of late apoptosis. The development of tumors following chemical cancerogenesis was significantly blunted by treatment with EMD638683.

Conclusions:

EMD638683 fosters suicidal death of colon tumor cells in vitro and decreases the number of colonic tumors following chemical cancerogenesis in vivo.