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  • Title: Ligands of peroxisome proliferator-activated receptor gamma induce apoptosis in multiple myeloma.
    Author: Eucker J, Bängeroth K, Zavrski I, Krebbel H, Zang C, Heider U, Jakob C, Elstner E, Possinger K, Sezer O.
    Journal: Anticancer Drugs; 2004 Nov; 15(10):955-60. PubMed ID: 15514564.
    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.
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