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Leuk Res. 2009 May;33(5):686-92. doi: 10.1016/j.leukres.2008.11.023. Epub 2009 Jan 7.

Compound 48, a novel dual PPAR alpha/gamma ligand, inhibits the growth of human CML cell lines and enhances the anticancer-effects of imatinib.

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Division of Hematology/Oncology, Universitätsmedizin Berlin Charité, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.


Compound 48 (C48) is a novel dual ligand for peroxisome proliferator-activated receptor alpha and gamma (PPAR alpha/gamma). Culture of imatinib-sensitive and -resistant CML cell lines with C48 resulted in a strong growth inhibition which associated with G0/G1 cell cycle arrest. However, it showed no obvious toxicity to normal CD34(+) hematopoietic stem cells. Decrease of pSTATs and pAKT were noticed suggesting that interference of AKT and STATs signaling may be the mechanisms for the effects of PPAR alpha/gamma ligands. Of more clinical importance, this ligand strongly enhanced the anticancer-effects of imatinib. Overall, our data suggest that the PPAR alpha/gamma ligands may have potentials in the treatment of CML in an adjuvant setting either before or after the development of imatinib resistance.

[Indexed for MEDLINE]

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