Department of Nutrition, Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.
Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.
J Cell Physiol. 2019 Mar;234(3):3029-3042. doi: 10.1002/jcp.27123. Epub 2018 Aug 26.
Antrodia salmonea is well known in Taiwan as a traditional Chinese medicinal fungus and has demonstrated antioxidant, anti-inflammatory, and anticancer effects. However, the anticancer activity of A. salmonea against human ovarian cancer is still elusive. Therefore, we investigated the antiovarian tumor activity of a fermented culture broth of A. salmonea and exhibits its underlying molecular mechanism. A. salmonea shows a significant effect on cell viability in human ovarian carcinoma (SKOV-3 or A2780) cell lines with an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Increased terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells and annexin V-propidium iodide stained cells indicate that A. salmonea induces late apoptosis in SKOV-3 cells. Notably, treatment with A. salmonea induced the following events: Apoptosis; caspase-3, -8, -9 and poly(ADP-ribose) polymerase activation; first apoptosis signal (Fas) and Fas ligand activation; Bid cleavage; and Bax2-B-cell lymphoma 2 dysregulation. The results show that A. salmonea-induced apoptosis was mediated by both mitochondrial and death receptor pathways. An increase in intracellular reactive oxygen species (ROS) was also observed in A. salmonea-treated cells, whereas the antioxidant N-acetylcysteine (NAC) prevented A. salmonea-induced cell death and DNA fragmentation, indicating that A. salmonea-induced apoptosis was mediated by ROS generation. Interestingly, A. salmonea-induced apoptosis is associated with the suppression of human epidermal growth factor receptor-2 (HER-2/neu) and phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) expression in HER-2/neu overexpressing SKOV-3 cells. NAC significantly prevented A. salmonea-induced HER-2/neu depletion and PI3K/AKT inactivation, indicating that A. salmonea-triggered apoptosis is mediated by ROS-inhibited HER-2/neu signaling cascades. To our knowledge, this is the first report describing the anticancer activity of this potentially beneficial mushroom against human ovarian carcinoma.
樟芝在台湾作为一种传统的中药真菌而闻名，具有抗氧化、抗炎和抗癌作用。然而，樟芝对人卵巢癌的抗癌活性仍不清楚。因此，我们研究了樟芝发酵培养物对人卵巢癌（SKOV-3 或 A2780）细胞系的抗肿瘤活性及其潜在的分子机制。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）检测结果表明，樟芝对人卵巢癌细胞系 SKOV-3 或 A2780 的细胞活力有显著影响。末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）阳性细胞和 Annexin V/碘化丙啶（PI）染色的细胞增加表明樟芝诱导 SKOV-3 细胞晚期凋亡。值得注意的是，用樟芝处理后，诱导以下事件发生：细胞凋亡；半胱天冬酶-3、-8、-9 和多聚（ADP-核糖）聚合酶的激活；第一凋亡信号（Fas）和 Fas 配体的激活；Bid 切割；以及 Bax2-B 细胞淋巴瘤 2 失调。结果表明，樟芝诱导的凋亡是通过线粒体和死亡受体途径介导的。在樟芝处理的细胞中也观察到细胞内活性氧（ROS）的增加，而抗氧化剂 N-乙酰半胱氨酸（NAC）可以防止樟芝诱导的细胞死亡和 DNA 片段化，表明樟芝诱导的凋亡是由 ROS 的产生介导的。有趣的是，樟芝诱导的凋亡与人类表皮生长因子受体-2（HER-2/neu）和磷酸肌醇 3-激酶（PI3K）-蛋白激酶 B（AKT）在 HER-2/neu 过表达 SKOV-3 细胞中的抑制有关。NAC 显著防止了樟芝诱导的 HER-2/neu 缺失和 PI3K/AKT 失活，表明樟芝触发的凋亡是由 ROS 抑制的 HER-2/neu 信号级联介导的。据我们所知，这是第一个描述这种潜在有益蘑菇对人卵巢癌的抗癌活性的报告。
