Hispolon Induces Apoptosis through JNK1/2-Mediated Activation of a Caspase-8,-9, and -3-Dependent Pathway in Acute Myeloid Leukemia (AML) Cells and Inhibits AML Xenograft Tumor Growth in Vivo
Hispolon Induces Apoptosis through JNK1/2-Mediated Activation of a Caspase-8,-9, and -3-Dependent Pathway in Acute Myeloid Leukemia (AML) Cells and Inhibits AML Xenograft Tumor Growth in Vivo
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DOI：
10.1021/jf402956m
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发表时间：
2013-10-23
影响因子：
6.1
通讯作者：
Chien, Ming-Hsien
中科院分区：
文献类型：
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作者：
Hsiao, Pei-Ching;Hsieh, Yi-Hsien;Chien, Ming-Hsien
Hispolon是桑黄的一种活性酚类化合物，桑黄是一种蘑菇，最近被证明在各种实体肿瘤中具有抗氧化和抗癌活性。在这里，我们研究了Hispolon在急性髓系白血病(AML)细胞中发挥抗癌作用的分子机制。结果表明，Hispolon对不同AML细胞系的细胞增殖均有抑制作用。此外，Hispolon通过激活caspase-8、-9和-3以及裂解PARP有效地诱导HL-60 AML细胞的凋亡。此外，Hispolon可诱导HL-60细胞持续激活JNK1/2，JNK1/2抑制剂或JNK1/2特异性siRNA抑制JNK可显著取消Hispolon诱导的caspase-8/-9/-3的激活。在体内，Hispolon显著减少了HL-60肿瘤移植瘤小鼠的肿瘤生长。在Hispolon治疗的肿瘤中，观察到caspase-3的激活和Ki67阳性细胞的减少。我们的结果表明，Hispolon可能有潜力成为治疗AML的工具。
Hispolon is an active phenolic compound of Phellinus igniarius, a mushroom that was recently shown to have antioxidant and anticancer activities in various solid tumors. Here, the molecular mechanisms by which hispolon exerts anticancer effects in acute myeloid leukemia (AML) cells was investigated. The results showed that hispolon suppressed cell proliferation in the various AML cell lines. Furthermore, hispolon effectively induced apoptosis of HL-60 AML cells through caspases-8, -9, and -3 activations and PARP cleavage. Moreover, treatment of HL-60 cells with hispolon induced sustained activation of JNK1/2, and inhibition of JNK by JNK1/2 inhibitor or JNK1/2-specific siRNA significantly abolished the hispolon-induced activation of the caspase-8/-9/-3. In vivo, hispolon significantly reduced tumor growth in mice with HL-60 tumor xenografts. In hispolon-treated tumors, activation of caspase-3 and a decrease in Ki67-positive cells were observed. Our results indicated that hispolon may have the potential to serve as a therapeutic tool to treat AML.