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

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-gamma (PPARgamma) and are killed by PPAR-gamma ligands. Herein. we investigate the therapeutic potential of PPAR-gamma ligands for multiple myeloma. The human multiple myeloma cell lines ANBL6 and 8226 express PPAR-gamma mRNA and protein. The PPAR-gamma ligands, 15-deoxy-Delta(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 PPAR-gamma 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 PPAR-gamma ligands greatly enhanced multiple myeloma cell killing. These new findings support that PPAR-gamma ligands may represent a novel therapy for multiple myeloma. (C) 2004 Elsevier Inc. All rights reserved.