Planta Med 2016; 82(S 01): S1-S381
DOI: 10.1055/s-0036-1596948
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

A-type proanthocyanidins selectively target acute myeloid leukemia cells in vitro and in vivo

LM Bystrom
1   Department of Medicine, Weill Cornell Medical College, 1300 York Ave, 10021 New York, USA
,
H Zong
1   Department of Medicine, Weill Cornell Medical College, 1300 York Ave, 10021 New York, USA
,
LAL Martinez
1   Department of Medicine, Weill Cornell Medical College, 1300 York Ave, 10021 New York, USA
,
C Neto
2   Department of Chemistry and Biochemistry, University of Massachusetts-Dartmouth, 285 Old Westport Road, 02747 North Dartmouth, USA
,
GJ Roboz
1   Department of Medicine, Weill Cornell Medical College, 1300 York Ave, 10021 New York, USA
,
S Rivella
3   Department of Pediatrics, University of Pennsylvania, 3620 Hamilton Walk, 19104 Philadelphia, USA
,
ML Guzman
1   Department of Medicine, Weill Cornell Medical College, 1300 York Ave, 10021 New York, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
14 December 2016 (online)

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Acute myelogenous leukemia (AML) is often a fatal disease where after strong induction therapy most patients relapse and die [1, 2]. A-type proanthocyanidins (A-PACs) are a unique class of compounds found in cranberries (Vaccinium macrocarpon Ait.) that we have found to be effective against several leukemia cell lines and primary AML samples in vitro. An A-PAC fraction, isolated from the cranberry powder CystiCran®40 (Naturex; Avignon, France), was found to selectively ablate leukemia stem and progenitor cells, with minimal effects on normal hematopoetic stem cells. Furthermore, AML engraftment of cells treated ex vivo with 62.5 µg/ml A-PACs was decreased compared to controls (90.6%, n = 3, P < 0.001), whereas normal CD34+ cells retained engraftment capability in immunodeficient mice. Administration of A-PACs to AML-patient derived xenotransplants (PDX) significantly reduced tumor burden in mice. Specifically, mice treated with 50 mg/kg and 25 mg/kg of A-PACs exhibited a 56.8% (n = 5) and 58.4% (n = 5) reduction in tumor burden, respectively, compared to the mice treated with the vehicle control (P < 0.05). These effects were better or equal to those observed in mice treated with high-dose cytarabine, a standard care drug. Moreover, no toxic effects were observed in the mice. These results indicate that A-PACs not only target primary AML cells in vitro, but are also effective in vivo by potentially a novel mechanism that may also target stem cells. Further elucidation of this mechanism may uncover new vulnerabilities of AML.

Acknowledgements: L.M. Bystrom was funded by NCCIH (award number F32AT007112) and M.L. Guzman was funded by the NIH Director's New Innovator Award Program (1 DP2 OD007399 – 01).

Keywords: Cranberry, leukemia, proanthocyanidins, xenotransplants.

References:

[1] Burnett A, Wetzler M, Lowenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol 2011; 29: 487 – 494

[2] Lowenberg B, Downing JR, Burnett A. Acute myeloid leukemia. N Engl J Med 1999; 341: 1051 – 1062