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PLoS One. 2017 Jul 20;12(7):e0181729. doi: 10.1371/journal.pone.0181729. eCollection 2017.

Active hexose-correlated compound enhances extrinsic-pathway-mediated apoptosis of Acute Myeloid Leukemic cells.

Author information

1
Medical Scientist Training Program, The Ohio State University, Columbus, Ohio, United States of America.
2
Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.
3
Center for Biostatistics, The Ohio State University, Columbus, Ohio, United States of America.
4
School of Arts and Sciences, Bluefield State University, Bluefield, WV, United States of America.

Abstract

Active Hexose Correlated Compound (AHCC) has been shown to have many immunostimulatory and anti-cancer activities in mice and in humans. As a natural product, AHCC has potential to create safer adjuvant therapies in cancer patients. Acute Myeloid Leukemia (AML) is the least curable and second-most common leukemia in adults. AML is especially terminal to those over 60 years old, where median survival is only 5 to 10 months, due to inability to receive intensive chemotherapy. Hence, the purpose of this study was to investigate the effects of AHCC on AML cells both in vitro and in vivo. Results showed that AHCC induced Caspase-3-dependent apoptosis in AML cell lines as well as in primary AML leukopheresis samples. Additionally, AHCC induced Caspase-8 cleavage as well as Fas and TRAIL upregulation, suggesting involvement of the extrinsic apoptotic pathway. In contrast, monocytes from healthy donors showed suppressed Caspase-3 cleavage and lower cell death. When tested in a murine engraftment model of AML, AHCC led to significantly increased survival time and decreased blast counts. These results uncover a mechanism by which AHCC leads to AML-cell specific death, and also lend support for the further investigation of AHCC as a potential adjuvant for the treatment of AML.

PMID:
28727820
PMCID:
PMC5519206
DOI:
10.1371/journal.pone.0181729
[Indexed for MEDLINE]
Free PMC Article

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