Can PPARγ Ligands Be Used in Cancer Therapy?
M. A.K. Rumi,
The role of peroxisome-proliferator activated receptor (PPAR)γ in tumor growth inhibition has been extensively studied during last seven years but still remains debated. Many in vitro and xenograft studies have demonstrated that PPARγ ligands are anti-tumorigenic due to anti-proliferative, pro-differentiation and anti-angiogenic effects. In animal models, PPARγ ligands have shown preventive effects against chemical carcinogenesis. On the other hand, evidences are accumulating against the possible use of this ligand activated nuclear receptor in molecular targeting for cancer therapy. The growth inhibitory effects of certain PPARγ ligands have recently been shown to be independent of PPARγ-activation. Studies have also come up with results indicating the growth promoting effects of PPARγ-activation, particularly in certain animal models genetically predisposed to cancer development. Loss-of-function mutations of PPARγ in tumors and increased susceptibility of PPARγ heterozygote knockout mice to carcinogenesis suggested a tumor-suppressing role of PPARγ. However, recent findings do not support PPARγ as a tumor suppressor gene. Although initial clinical trials with PPARγ ligand troglitazone reported promising results in liposarcoma and prostate cancers, recent studies failed to show the expected therapeutic values in advanced colorectal and breast cancers. In this review, we have addressed these controversies on potential use of PPARγ ligands in cancer therapy.
Keywords: peroxisome-proliferator activated receptor (ppar), animal model of carcinogenesis, and growth-inhibition versus growth-promotion
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