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

Kavin Fatehchand,Xiaokui Mo,Ericka L Erickson,Jonathan P Butchar,Ramasamy Santhanam,Shalini Gautam,Susheela Tridandapani,Brenda Shen,Tesfaye Belay,Saranya Elavazhagan,Francesco Bertolini

doi:10.1371/journal.pone.0181729

Kavin Fatehchand, Xiaokui Mo + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0181729

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Journal: PloS one	Publication Date: Jul 20, 2017
Citations: 12	License type: CC BY 4.0

Affiliation: The Ohio State University

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.

Highlights

Acute Myeloid Leukemia (AML) is the most common type of acute leukemia in adults, causing over 10,500 deaths and affecting over 20,000 people in 2015 [1,2,3]
We found that treatment of AML cell lines and primary AML leukopheresis samples with Active Hexose Correlated Compound (AHCC) led to an increase in apoptosis, which was Caspase-3-dependent
Annexin/Propidium Iodide (PI) staining showed that AHCC led to apoptosis in OCI-AML3 and MOLM-13 but not in THP-1 cells (Fig 2B)

Summary

Introduction

Acute Myeloid Leukemia (AML) is the most common type of acute leukemia in adults, causing over 10,500 deaths and affecting over 20,000 people in 2015 [1,2,3]. This disease is characterized by an infiltration of the bone marrow, blood, and other tissues by myeloid precursors, or “blasts,” which are unable to differentiate [4]. Despite multiple biologically-distinct subtypes of AML, the current methodology of treatment includes a regimen of chemotherapy and stem cell transplant [5].

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