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Ligands of peroxisome proliferator-activated receptor gamma induce apoptosis in multiple myeloma

Jan Eucker1, Katharina Bängeroth, Ivana Zavrski

  • 1Department of Oncology and Hematology, University Hospital Charité, Berlin, Germany.

Anti-Cancer Drugs
|October 30, 2004
PubMed

Insights

The natural activator 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) and thiazolidinediones inhibit multiple myeloma cell growth. 15d-PGJ2 effectively induced apoptosis in myeloma cells, suggesting therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Proliferator-activated receptor gamma (PPAR-gamma) activation induces apoptosis in various cancer cells.
  • Multiple myeloma is a malignant B-cell neoplasm characterized by uncontrolled plasma cell proliferation.

Purpose of the Study:

  • To investigate the anti-myeloma activity of PPAR-gamma activators, including 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) and thiazolidinediones (pioglitazone, rosiglitazone).
  • To evaluate the effect of these compounds on multiple myeloma cell lines and primary patient cells.

Main Methods:

  • Treatment of five human multiple myeloma cell lines and primary bone marrow myeloma cells with 15d-PGJ2, pioglitazone, and rosiglitazone.
  • Assessment of cell growth inhibition using MTT assays.
  • Quantification of apoptosis induction via Annexin-V staining.

Main Results:

  • 15d-PGJ2 demonstrated significant dose-dependent growth arrest and induced high rates of apoptosis (60-92%) in all tested myeloma cell lines.
  • Thiazolidinediones (pioglitazone and rosiglitazone) exhibited a lower antiproliferative effect compared to 15d-PGJ2.
  • Apoptosis was also induced in sorted bone marrow plasma cells from multiple myeloma patients.

Conclusions:

  • PPAR-gamma activators, particularly 15d-PGJ2, show potent in vitro anti-myeloma activity.
  • Thiazolidinediones possess anti-myeloma effects that warrant further investigation for therapeutic applications.
  • These findings suggest a potential role for PPAR-gamma modulation in multiple myeloma treatment.

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