Cell death susceptibility of human glioma cells to Bortezomib treatment is R-CRT regulated

ANDREA COMBA; VICTOR E. GOITEA; MAURICIO R. GALIANO; MARTA E. HALLAK

Mar del Plata

Congreso; XXX Congreso Anual de la Sociedad Argentina de Investigacion en Neurociencias; 2015

Sociedad Argentina de Investigacion en Neurociencias

Previously, we described that calreticulin is posttranslational arginilated (R-CRT) by the enzyme ATE1. Different functions have been proposed to R-CRT as it was found associated with stress granules (SGs) and at the plasma membrane, where it participates in pro-apoptotic events. The apoptosis resistance of different cancer cells to treatment with therapeutic drugs as Bortezomib has been associated with SGs formation. In this study we evaluated if R-CRT modulates the apoptosis susceptibility of different glioma cells treated with Bortezomib. A difference was observed after treatment between HOG and MO59K cell lines, HOG cells showed reduced cell viability and increased levels of cleaved caspase-3 whereas MO59K cells were more resistant to the drug. Also, increased levels of R-CRT were determined in the cytosol and at cell membrane in HOG cells after treatment, but not in the MO59K cells. Additionally, by confocal analysis we measured that only in MO59K cells treated with Bort ezomib showed an increased formation of SGs and an augmented cytosolic association of R-CRT to SGs. These results are suggestive that R-CRT up-regulation and its subcellular localization could be involved in caspase-3 dependent cell death response of human glioma cell lines to Bortezomib treatment. Hence R-CRT is a protein that could have an influence on brain cancer treatment.