Li Xiaohui, Zhao Xin, Wang Hongmin, Han Junqing, Liu Li
The Center of Tumor Research and Therapy, Shandong Provincial Hospital to Shandong University, Jinan, 250021, Shandong Province, China.
Tumour Biol. 2014 Sep;35(9):8963-8. doi: 10.1007/s13277-014-2137-0. Epub 2014 Jun 6.
Polysaccharides are the major active ingredients of fungus Agaricus blazei for treating and preventing cancer. However, there are no reports showing anti-tumor activity of A. blazei polysaccharides (ABP) on human leukemia (HL)-60 cells in vitro and in vivo. In this study, we demonstrated that ABP efficiently inhibited proliferation of cultured HL-60 cells, which was associated with the induction of apoptosis. The increase in ABP-induced apoptosis was accompanied by loss of mitochondria membrane potential (∆Ψm), cytochrome c release from the mitochondria, activation of caspase-3, degradation of poly(ADP-ribose) polymerase (PARP), and the elevated ratio of Bcl-2-associated X (Bax)/B-cell lymphoma 2 (Bcl-2). Moreover, z-DEVD-fmk, a caspase-3 inhibitor, reversed the cytotoxic effects and apoptotic characteristics induced by ABP in HL-60 cells. Furthermore, we confirmed that ABP could obviously inhibit the solid cancer growth of leukemia HL-60 in tumor xenograft model. These data demonstrated that ABP effectively induced the apoptosis of HL-60 cells via a signaling cascade of mitochondrial caspase-3-dependent pathway.
多糖是姬松茸治疗和预防癌症的主要活性成分。然而，尚无关于姬松茸多糖（ABP）在体外和体内对人白血病（HL）-60细胞抗肿瘤活性的报道。在本研究中，我们证明ABP能有效抑制培养的HL-60细胞增殖，这与诱导细胞凋亡有关。ABP诱导的细胞凋亡增加伴随着线粒体膜电位（∆Ψm）丧失、细胞色素c从线粒体释放、半胱天冬酶-3激活、聚（ADP-核糖）聚合酶（PARP）降解以及Bcl-2相关X蛋白（Bax）/B细胞淋巴瘤2蛋白（Bcl-2）比值升高。此外，半胱天冬酶-3抑制剂z-DEVD-fmk可逆转ABP诱导的HL-60细胞的细胞毒性作用和凋亡特征。此外，我们证实ABP在肿瘤异种移植模型中能明显抑制白血病HL-60实体瘤生长。这些数据表明，ABP通过线粒体半胱天冬酶-3依赖性信号级联有效地诱导HL-60细胞凋亡。
