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Peroxisome Proliferator‐Activated Receptor Ligands and Their Role in Chronic Myeloid Leukemia: Therapeutic Strategies
Author(s) -
Yousefi Bahman,
Samadi Nasser,
Baradaran Behzad,
ShafieiIrannejad Vahid,
Zarghami Nosratollah
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12737
Subject(s) - myeloid leukemia , imatinib , cancer research , receptor , peroxisome proliferator activated receptor , imatinib mesylate , pharmacology , myeloid , leukemia , tyrosine kinase , chemistry , biology , immunology , biochemistry
Imatinib therapy remains the gold standard for treatment of chronic myeloid leukemia; however, the acquired resistance to this therapeutic agent in patients has urged the scientists to devise modalities for overcoming this chemoresistance. For this purpose, initially therapeutic agents with higher tyrosine kinase activity were introduced, which had the potential for inhibiting even mutant forms of Bcr‐Abl. Furthermore, coupling imatinib with peroxisome proliferator‐activated receptor ligands also showed beneficial effects in chronic myeloid leukemia cell proliferation. These combination protocols inhibited cell growth and induced apoptosis as well as differentiation in chronic myeloid leukemia cell lines. In addition, peroxisome proliferator‐activated receptors ligands increased imatinib uptake by upregulating the expression of human organic cation transporter 1. Taken together, peroxisome proliferator‐activated receptors ligands are currently being considered as novel promising therapeutic candidates for chronic myeloid leukemia treatment, because they can synergistically enhance the efficacy of imatinib. In this article, we reviewed the potential of peroxisome proliferator‐activated receptors ligands for use in chronic myeloid leukemia treatment. The mechanism of action of these therapeutics modalities are also presented in detail.