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

Multiple myeloma (MM) is characterised by intense protein folding and, consequently endoplasmic reticulum (ER) stress. The prostaglandin 15d-PGJ 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 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 at 1-10μM 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 at 4mg/kg or vehicle (control), with tumour volume being monitored for 14days. 15d-PGJ reduced cell proliferation, induced cell death and apoptosis at 5μM and 10μM and Stress-related genes were upregulated at the same doses. Oxidized glutathione levels were also increased. 15d-PGJ2 at 4mg/kg in vivo halted tumour growth. In conclusion, 15d-PGJ induced myeloma cell death via ER stress in vitro. 15d-PGJ2 in vivo also inhibited tumour growth.