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

Compound 48 (C48) is a novel dual ligand for peroxisome proliferator-activated receptor α and γ (PPARα/γ). 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 PPARα/γ ligands. Of more clinical importance, this ligand strongly enhanced the anticancer-effects of imatinib. Overall, our data suggest that the PPARα/γ ligands may have potentials in the treatment of CML in an adjuvant setting either before or after the development of imatinib resistance.