Human multiple myeloma cells express peroxisome proliferator-activated receptor γ and undergo apoptosis upon exposure to PPARγ ligands

Abstract

Multiple myeloma is essentially an incurable malignancy and it is therefore of great interest to develop new therapeutic approaches. We previously reported that human B cell-lymphomas express the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) and are killed by PPARγ ligands. Herein, we investigate the therapeutic potential of PPARγ ligands for multiple myeloma. The human multiple myeloma cell lines ANBL6 and 8226 express PPARγ mRNA and protein. The PPARγ ligands, 15-deoxy-Δ 12,14-prostaglandin J 2 (15d-PGJ 2) and ciglitazone, induced multiple myeloma cell apoptosis as determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, loss of mitochondrial membrane potential, and caspase activation. Importantly, the ability of PPARγ ligands to kill both multiple myeloma cell lines was not abrogated by Interleukin-6 (IL-6), a multiple myeloma growth survival factor. Finally, the RXR ligand 9-cis retinoic acid (9-cis RA) in combination with PPARγ ligands greatly enhanced multiple myeloma cell killing. These new findings support that PPARγ ligands may represent a novel therapy for multiple myeloma.