Ligands of peroxisome proliferator-activated receptor gamma induce apoptosis in multiple myeloma.
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.
Eucker
Jan
J
Department of Oncology and Hematology, University Hospital Charité, Berlin, Germany.
Bängeroth
Katharina
K
Zavrski
Ivana
I
Krebbel
Holger
H
Zang
Chuanbing
C
Heider
Ulrike
U
Jakob
Christian
C
Elstner
Elena
E
Possinger
Kurt
K
Sezer
Orhan
O
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*
C477819:15-deoxyprostaglandin J2; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D015230:Prostaglandin D2; D000077205:Pioglitazone