15d-PGJ(2) as an endoplasmic reticulum stress manipulator in multiple myeloma in vitro and in vivo

Author(s):Show less -

Sperandio, Marcelo ; Demasi, Ana Paula D. ; Martinez, Elizabeth F. ; Saad, Sara O. ; Pericole, Fernando V. ; Vieira, Karla P. ; Freitas, Nadir S. ; Araujo, Vera C. ; Brown, Amy Louise ; Clemente-Napimoga, Juliana Trindade ; Napimoga, Marcelo Henrique

• Document type: Journal article
• Source: Experimental and Molecular Pathology; v. 102, n. 3, p. 434-445, JUN 2017.
• Web of Science Citations: 4

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 mu M 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 mu M and 10 mu M and Stress-related genes were upregulated at the same doses. Oxidized glutathione levels were also increased. 15d-PGJ(2) at 4 mg/kg in vivo halted tumour growth. In conclusion, 15d-PGJ(2) induced myeloma cell death via ER stress in vitro. 15d-PGJ(2) in vivo also inhibited tumour growth. (AU)

• FAPESP's process: 13/02347-8 - The effect of 15d-PGJ2 on multiple myeloma cell line development in vitro and in vivo
• Grantee: Marcelo Sperandio
• Support Opportunities: Scholarships in Brazil - Post-Doctoral