Cranberry A-type proanthocyanidins selectively target acute myeloid leukemia cells
| Autor: | Monica L. Guzman, Luis A. Lara-Martinez, Stefano Rivella, Hsiao-Ting Hsu, Sara Gardenghi, Jeanne P. De Leon, Hongliang Zong, Daniel P. Bezerra, Laura M. Bystrom, Duane C. Hassane, Michael W. Becker, David E Mery, Susanna Cunningham-Rundles, Catherine C. Neto, Megan Emmanuel |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
RM Myeloid Cell Survival CD34 RV Q1 03 medical and health sciences Mice 0302 clinical medicine Cell Line Tumor medicine Animals Humans Proanthocyanidins Dose-Response Relationship Drug business.industry Plant Extracts Myeloid leukemia Hematology medicine.disease R1 Antineoplastic Agents Phytogenic Xenograft Model Antitumor Assays Stimulus Report humanities Leukemia Haematopoiesis Disease Models Animal Leukemia Myeloid Acute 030104 developmental biology medicine.anatomical_structure Vaccinium macrocarpon Cell culture 030220 oncology & carcinogenesis Cord blood Cancer research Stem cell business RB |
| Zdroj: | Blood advances. 3(21) |
| ISSN: | 2473-9537 2473-9529 |
| Popis: | Most elderly patients affected with acute myeloid leukemia (AML) will relapse and die of their disease even after achieving complete remission, thus emphasizing the urgent need for new therapeutic approaches with minimum toxicity to normal hematopoietic cells. Cranberry (Vaccinium spp.) extracts have exhibited anticancer and chemopreventive properties that have been mostly attributed to A-type proanthocyanidin (A-PAC) compounds. A-PACs, isolated from a commercially available cranberry extract, were evaluated for their effects on leukemia cell lines, primary AML samples, and normal CD34(+) cord blood specimens. Our results indicated potent and specific antileukemia activity in vitro. In addition, the antileukemia activity of A-PACs extended to malignant progenitor and stem cell populations, sparing their normal counterparts. The antileukemia effects of A-PACs were also observed in vivo using patient derived xenografts. Surprisingly, we found that the mechanism of cell death was driven by activation of NF-κB. Overall, our data suggest that A-PACs could be used to improve treatments for AML by targeting leukemia stem cells through a potentially novel pathway. |
| Databáze: | OpenAIRE |
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