Resveratrol enhances the suppressive effects of arsenic trioxide on primitive leukemic progenitors

Abstract

Efforts to enhance the antileukemic properties of arsenic trioxide are clinically relevant and may lead to the development of new therapeutic approaches for the management of certain hematological malignancies. We provide evidence that concomitant treatment of acute myeloid leukemia (AML) cells or chronic myeloid leukemia (CML) cells with resveratrol potentiates arsenic trioxide-dependent induction of apoptosis. Importantly, clonogenic assays in methylcellulose demonstrate potent suppressive effects of the combination of these agents on primitive leukemic progenitors derived from patients with AML or CML. Taken together, these findings suggest that combinations of arsenic trioxide with resveratrol may provide an approach for targeting of early leukemic precursors and, possibly, leukemia initiating stem cells.

Keywords: :

• arsenic trioxide
• myeloid leukemia
• apoptosis
• autophagy

10.4161/cbt.27824

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

This work was supported by National Institutes of Health grants CA121192, CA155566, CA77816, and CA174205; and by grant I01CX000916 from the Department of Veterans Affairs. E.B. was supported by NIH training grant T32CA070085.