Compound 48, a novel dual PPAR α/γ ligand, inhibits the growth of human CML cell lines and enhances the anticancer-effects of imatinib
✍ Scribed by Janina Bertz; Chuanbing Zang; Hongyu Liu; Marlies Wächter; Kurt Possinger; H. Phillip Koeffler; Elena Elstner
- Book ID
- 104040920
- Publisher
- Elsevier Science
- Year
- 2009
- Tongue
- English
- Weight
- 763 KB
- Volume
- 33
- Category
- Article
- ISSN
- 0145-2126
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✦ Synopsis
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.