title: Ligands of peroxisome proliferator-activated receptor gamma induce apoptosis in multiple myeloma.
abstract: The activation of proliferator-activated receptor gamma (PPAR-gamma) by its natural and synthetic ligands induces apoptosis in several tumor cell lines, including malignant B-lineage cells. We investigated whether treatment with pioglitazone (PGZ), rosiglitazone (RGZ) or 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) inhibited tumor cell growth in five human multiple myeloma cell lines (LP-1, U-266, RPMI-8226-S, OPM-2 and IM-9) and human bone marrow myeloma cells expressing PPAR-gamma protein. MTT assays revealed growth arrest induced by the natural activator of PPAR-gamma 15d-PGJ2 and a lower antiproliferative effect with thiazolidinediones (PGZ and RGZ) in a dose-dependent manner. Induction of apoptosis was indicated by Annexin-V staining. At a dose of 50 microM, 15d-PGJ2 led to a high rate of apoptosis in all cell lines (60-92%). Furthermore, induction of apoptosis in sorted bone marrow plasma cells from myeloma patients was detected. Thiazolidinediones comprise anti-myeloma activity in vitro and should be explored further for the treatment of multiple myeloma.
authors.affiliation: Department of Oncology and Hematology, University Hospital Charité, Berlin, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Eucker
authors.forename: Katharina
authors.initials: K
authors.lastname: Bängeroth
authors.forename: Ivana
authors.initials: I
authors.lastname: Zavrski
authors.forename: Holger
authors.initials: H
authors.lastname: Krebbel
authors.forename: Chuanbing
authors.initials: C
authors.lastname: Zang
authors.forename: Ulrike
authors.initials: U
authors.lastname: Heider
authors.forename: Christian
authors.initials: C
authors.lastname: Jakob
authors.forename: Elena
authors.initials: E
authors.lastname: Elstner
authors.forename: Kurt
authors.initials: K
authors.lastname: Possinger
authors.forename: Orhan
authors.initials: O
authors.lastname: Sezer
mesh_terms: D017209:Apoptosis; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008024:Ligands; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: C477819:15-deoxyprostaglandin J2; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D015230:Prostaglandin D2; D000077205:Pioglitazone