Deferasirox has strong anti-leukemia activity but may antagonize theanti-leukemia effect of doxorubicin

Abstract

Deferasirox (DFX), in addition to its iron-chelation property, has marked anti-proliferative effects on cancer cells. However, the activity and mechanism by which DFX inhibits acute myeloid leukemia (AML) cells remain to be elucidated. Furthermore, the anti-leukemia effect of combining DFX with currently recommended agents doxorubicin (DOX) and cytosine arabinoside (Ara-C) has not been studied. In this study, we show that DFX significantly reduces the viability of three AML cell lines, HL60, THP1, and WEHI3 and two primary leukemic cells harvested from AML patients. DFX induces cell cycle arrest at G1 phase and apoptosis and inhibits phosphorylation of ERK. We also showed that DFX antagonizes the anti-leukemic effect of DOX. On the contrary, combining DFX with Ara-C created a synergistic effect. Our study confirms the anti-leukemia activity of DFX and provides important information on how to select a partner drug for DFX for the treatment of AML in future clinical trials.

Keywords:

• Deferasirox
• AML
• doxorubicin
• Ara-C

Acknowledgements

This work was supported in part by the research grant from National Science Council of Taiwan (NSC-101-2321-B-039-005), and China Medical University Hospital (DMR-105-017).

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2017.1280604.

Additional information

Funding

This work was supported in part by the research grant from National Science Council of Taiwan (NSC-101-2321-B-039-005), and China Medical University Hospital (DMR-105-017).