Peroxisome proliferator-activated receptor-gamma ligands inhibit proliferation and induce apoptosis in mantle cell lymphoma.
Peroxisome proliferator-activated receptor-gamma, a nuclear receptor and transcription factor, and its natural and synthetic ligands have become a focus of novel approaches to induction of apoptosis in solid tumors and hematologic malignancies, including malignant B-lineage cells. The effect on mantle cell lymphoma, a subtype with dismal prognosis, has not yet been analyzed. We investigated the effect of 15-deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2), pioglitazone (PGZ) or rosiglitazone (RGZ) on human mantle cell lymphoma cell lines (GRANTA-519, Hbl-2 and JeKo-1). Mantle cell lymphoma cell lines exhibited a high expression of Peroxisome proliferator-activated receptor-gamma protein in Western blot analysis. MTT assays revealed anti-proliferative effects induced by both 15d-PGJ2, the natural activator of Peroxisome proliferator-activated receptor-gamma, and PGZ and RGZ, synthetic Peroxisome proliferator-activated receptor-gamma ligands, in a dose-dependent manner. At a dose of 50 micromol/l, 15d-PGJ2 induced growth inhibition in all cell lines. The anti-proliferative effect of PGZ and RGZ was slightly lower. Induction of apoptosis was indicated by annexin V staining. At a dose of 50 micromol/l, 15d-PGJ2 led to apoptosis in all cell lines (87-99%) after 48 h of incubation. Again, the apoptotic effect with thiazolidinediones was slightly lower at the same dose level. This is the first study evaluating Peroxisome proliferator-activated receptor-gamma expression and its therapeutic implications in human mantle cell lymphoma cells. Thiazolidinediones comprise anti-lymphoma activity in vitro and should be further explored for the treatment of mantle cell lymphoma.
Eucker
Jan
J
Department of Oncology and Hematology, University Hospital Charité, Berlin, Germany.
Sterz
Jan
J
Krebbel
Holger
H
Zavrski
Ivana
I
Kaiser
Martin
M
Zang
Chuanbing
C
Heider
Ulrike
U
Jakob
Christian
C
Elstner
Elena
E
Sezer
Orhan
O
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D006801:Humans; D008024:Ligands; D020522:Lymphoma, Mantle-Cell / Q000473:pathology*; D047495:PPAR gamma / Q000187:drug effects*; D000077205:Pioglitazone; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D017304:Annexin A5; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019938:Cyclin D1; D015230:Prostaglandin D2; D000077205:Pioglitazone