Human multiple myeloma cells express peroxisome proliferator-activated receptor gamma and undergo apoptosis upon exposure to PPARgamma ligands |
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Authors: | Ray Denise M Bernstein Steven H Phipps Richard P |
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Affiliation: | The Lung Biology and Disease Program, Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, NY 14642, USA. |
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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 gamma (PPARgamma) and are killed by PPARgamma ligands. Herein, we investigate the therapeutic potential of PPARgamma ligands for multiple myeloma. The human multiple myeloma cell lines ANBL6 and 8226 express PPARgamma mRNA and protein. The PPARgamma ligands, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) 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 PPARgamma 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 PPARgamma ligands greatly enhanced multiple myeloma cell killing. These new findings support that PPARgamma ligands may represent a novel therapy for multiple myeloma. |
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Keywords: | PPARγ peroxisome proliferator-activated receptor γ IL-6 Interleukin-6 IMiDs immunomodulatory thalidomide analogs TZD thiazolidinedione RXR retinoid X receptor (9-cis RA receptor) 9-cis RA 9-cis retinoic acid TUNEL terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling Myeloma Apoptosis Prostaglandins PPARγ Thiazolidinedione |
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