Active hexose-correlated compound enhances extrinsic-pathway-mediated apoptosis of Acute Myeloid Leukemic cells.
Active hexose-correlated compound enhances extrinsic-pathway-mediated apoptosis of Acute Myeloid Leukemic cells.
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DOI：
10.1371/journal.pone.0181729
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Butchar JP
中科院分区：
文献类型：
--
作者：
Fatehchand K;Santhanam R;Shen B;Erickson EL;Gautam S;Elavazhagan S;Mo X;Belay T;Tridandapani S;Butchar JP
活性己糖相关化合物（AHCC）已被证明在小鼠和人类中具有许多免疫刺激和抗癌活性。作为一种天然产物，AHCC有潜力为癌症患者创造更安全的辅助治疗。急性髓系白血病（AML）是成人中最难治愈和第二常见的白血病。AML对于60岁以上的患者尤其是晚期，由于无法接受强化化疗，中位生存期仅为5至10个月。因此，本研究的目的是研究AHCC在体外和体内对AML细胞的影响。结果显示，AHCC在AML细胞系和原代AML白细胞去除样本中诱导了Caspase-3依赖性细胞凋亡。此外，AHCC诱导Caspase-8裂解以及Fas和TRAIL上调，表明参与了外源性凋亡途径。相比之下，来自健康供体的单核细胞显示出抑制的胱天蛋白酶-3切割和较低的细胞死亡。当在AML的小鼠移植模型中测试时，AHCC导致存活时间显著增加和原始细胞计数减少。这些结果揭示了AHCC导致AML细胞特异性死亡的机制，也为进一步研究AHCC作为治疗AML的潜在佐剂提供了支持。
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.
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