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Active hexose-correlated compound enhances extrinsic-pathway-mediated apoptosis of Acute Myeloid Leukemic cells.
- Source :
-
PloS one [PLoS One] 2017 Jul 20; Vol. 12 (7), pp. e0181729. Date of Electronic Publication: 2017 Jul 20 (Print Publication: 2017). - Publication Year :
- 2017
-
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.
- Subjects :
- Animals
Apoptosis physiology
Blotting, Western
Caspase 3 metabolism
Caspase 8 metabolism
Cell Line, Tumor
Cell Survival drug effects
Cell Survival physiology
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Female
Leukemia, Myeloid, Acute metabolism
Mice, SCID
Monocytes drug effects
Monocytes metabolism
Neoplasm Transplantation
Real-Time Polymerase Chain Reaction
TNF-Related Apoptosis-Inducing Ligand metabolism
fas Receptor metabolism
Antineoplastic Agents pharmacology
Apoptosis drug effects
Leukemia, Myeloid, Acute drug therapy
Polysaccharides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 12
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 28727820
- Full Text :
- https://doi.org/10.1371/journal.pone.0181729