15d-PGJ2 as an endoplasmic reticulum stress manipulator in multiple myeloma in vitro and in vivo

Abstract Multiple myeloma (MM) is characterised by intense protein folding and, consequently endoplasmic reticulum (ER) stress. The prostaglandin 15d-PGJ 2 is able to raise oxidative stress levels within the cell and potentially trigger cell death. The aim of this study was to evaluate the antineoplastic effect of 15d-PGJ 2 on MM in vitro and in vivo via ER and oxidative stress pathways. MM.1R and MM.1S cell lines were treated with 15d-PGJ 2 at 1–10 μM and evaluated with regard to proliferation, mRNA expression of PRDX1 , PRDX4 , GRP78 , GRP94 , CHOP , BCL-2 and BAX . Stress data was validated via oxidized glutathione assays. MM.1R cells were inoculated into NOD/SCID mice, which were subsequently treated daily with 15d-PGJ 2 at 4 mg/kg or vehicle (control), with tumour volume being monitored for 14 days. 15d-PGJ 2 reduced cell proliferation, induced cell death and apoptosis at 5 μM and 10 μM and Stress-related genes were upregulated at the same doses. Oxidized glutathione levels were also increased. 15d-PGJ2 at 4 mg/kg in vivo halted tumour growth. In conclusion, 15d-PGJ 2 induced myeloma cell death via ER stress in vitro . 15d-PGJ2 in vivo also inhibited tumour growth.