School of Medicine, ‡Institute of Biochemistry and Biotechnology, and §Institute of Medicine, Chung Shan Medical University , No. 110, Section 1, Chien-Kuo N Road, Taichung 40201, Taiwan.
J Agric Food Chem. 2013 Oct 23;61(42):10063-73. doi: 10.1021/jf402956m. Epub 2013 Oct 15.
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.
棘孢木层孔菌是木层孔菌属的一种真菌，具有抗氧化和抗癌活性，可用于多种实体肿瘤的治疗。本文研究了棘孢木层孔菌在急性髓细胞白血病（AML）细胞中的抗癌作用机制。结果表明，棘孢木层孔菌可抑制多种 AML 细胞系的细胞增殖。此外，棘孢木层孔菌可通过激活半胱天冬酶-8、-9 和 -3 以及多聚（ADP-核糖）聚合酶的切割有效诱导 HL-60 AML 细胞凋亡。此外，用棘孢木层孔菌处理 HL-60 细胞可诱导 JNK1/2 的持续激活，JNK1/2 抑制剂或 JNK1/2 特异性 siRNA 抑制 JNK1/2 可显著消除棘孢木层孔菌诱导的半胱天冬酶-8/-9/-3 激活。在体内，棘孢木层孔菌可显著减少 HL-60 肿瘤异种移植小鼠的肿瘤生长。在棘孢木层孔菌处理的肿瘤中，观察到 caspase-3 的激活和 Ki67 阳性细胞的减少。这些结果表明，棘孢木层孔菌可能具有作为治疗 AML 的治疗工具的潜力。
