Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, 40402, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung, 41354, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung, 40402, Taiwan; Research Center of Chinese Herbal Medicine, China Medical University, Taichung, 40402, Taiwan.
Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, 40402, Taiwan.
Food Chem Toxicol. 2019 Feb;124:30-44. doi: 10.1016/j.fct.2018.11.043. Epub 2018 Nov 19.
The medicinal fungus Ganoderma, known in Chinese as Lingzhi or Reishi, traditionally has various medicinal uses and has been employed in cancer treatment in Asia for centuries. This study used ethanol-extracted Ganoderma tsugae (GT) and examined its antitumor activities on human chronic myeloid leukemia cells as well as its molecular mechanism of action. Treatment with GT (200-400 μg/mL) significantly reduced cell viability and caused G2/M arrest in K562 cells. In addition, GT induced mitochondrial and death receptor mediated apoptosis, correlated with DNA fragmentation, followed by cytochrome c release, caspase-3/8/9 activation, PARP cleavage, Fas activation, Bid cleavage, and Bax/Bcl-2 dysregulation. Cytoprotective autophagy was found to be induced by GT, as was revealed by increased LC3-II accumulation, Beclin-1/Bcl-2 dysregulation, acidic vesicular organelle formation, and p62/SQSTM1 activation. Notably, pretreatment of cells with the autophagy inhibitors 3-MA and CQ enhanced GT-induced apoptosis. Interestingly, reactive oxygen species production in cells was not triggered by GT administration; equally, the antioxidant N-acetylcysteine was found to be incapable of preventing apoptosis and autophagy induced by GT treatment. Finally, this study discovered that cytoprotective autophagy induced by GT was associated with EGFR and PI3K/AKT/mTOR signaling cascade suppression. In summary, GT demonstrated antitumor activity against human chronic myeloid leukemia.
药用真菌灵芝，中文名为 Lingzhi 或 Reishi，传统上具有多种药用功效，并在亚洲用于癌症治疗已有数百年的历史。本研究使用乙醇提取的云芝（GT），并研究了其对人慢性髓系白血病细胞的抗肿瘤活性及其作用机制。GT（200-400μg/ml）处理显著降低 K562 细胞的活力并导致 G2/M 期阻滞。此外，GT 诱导线粒体和死亡受体介导的细胞凋亡，与 DNA 片段化相关，随后发生细胞色素 c 释放、caspase-3/8/9 激活、PARP 切割、Fas 激活、Bid 切割和 Bax/Bcl-2 失调。发现 GT 诱导细胞发生细胞保护性自噬，表现为 LC3-II 积累增加、Beclin-1/Bcl-2 失调、酸性囊泡细胞器形成和 p62/SQSTM1 激活。值得注意的是，用自噬抑制剂 3-MA 和 CQ 预处理细胞可增强 GT 诱导的细胞凋亡。有趣的是，GT 处理不会引发细胞中活性氧的产生；同样，抗氧化剂 N-乙酰半胱氨酸也不能防止 GT 处理诱导的细胞凋亡和自噬。最后，本研究发现 GT 诱导的细胞保护性自噬与 EGFR 和 PI3K/AKT/mTOR 信号级联的抑制有关。总之，GT 对人慢性髓系白血病具有抗肿瘤活性。
