Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Neurosurgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
Department of Pediatrics, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
J Ethnopharmacol. 2017 Jul 31;207:47-56. doi: 10.1016/j.jep.2017.06.004. Epub 2017 Jun 8.
The discovery of many tissue-specific cancer stem cells (CSCs) continues to attract scientific attention. These CSCs are considered to be associated with chemo- and radio-resistance, and consequently, failure of conventional anticancer therapies. The recent demonstration of several microRNAs as enhancers of tumorigenicity via modulation of epithelial-mesenchymal transition and cancer stemness, makes them putative novel therapeutic target in oncology. Antrodia cinnamomea is a Chinese traditional medicine with several biological functions including anti-inflammation, antioxidant, and cancer prevention. However, the anti-CSC capability of A. Cinnamomea is not clear yet.
To investigate the inhibitory effect of A. cinnamomea mycelium and extract on CSCs derived from various human cancer cell lines using our in-house therapeutics and human genome-wide miRNA screening panels.
A broad range of human cancer cell lines, including the acute monocytic leukemia (THP-1), glioblastoma multiforme (GBM 8401), lung carcinoma (A549), breast adenocarcinoma (MDA-MB-231), hepatoblastoma (HepG2), colorectal adenocarcinoma (SW620), and foreskin fibroblast (HS68), were exposed to A. cinnamomea in this study. CD133 CSCs generated from the cell lines were characterized and isolated by flow cytometry, effect of chemo- and radiotherapy was assessed using the MTT assay, while the RT-PCR and human genome wide qRT-PCR determined the differential gene expression patterns. A comparative analysis of the anticancer effect of A. cinnamomea and Cisplatin, Taxol, or irradiation was also performed.
Our results indicated that A. cinnamomea mycelium and its ethyl acetate extracts showed anti-proliferation effects against all types of CSCs, especially the lung, breast, and head and neck squamous cell carcinoma CSCs. Furthermore, CSCs treatment with A. cinnamomea combined with irradiation or chemotherapeutics demonstrated significant anti-cancer effect. We also established an association between the CSC-inhibitory effect of A. cinnamomea and significant downregulation of several microRNAs and cancer stemness expression levels in brain and breast CSCs. More importantly, higher CD133 expression is associated with poor prognosis in glioblastoma and breast cancer patients.
Herein, we demonstrate the putative role of A. cinnamomea as an effective ethnopharmacologic therapeutic agent for cancer treatment.
不断有研究发现多种组织特异性的癌症干细胞（CSC），这持续吸引着科学界的关注。这些 CSC 被认为与化疗和放疗耐药性有关，进而导致传统抗癌疗法失败。最近的研究表明，多种 microRNAs 通过调节上皮间质转化和癌症干细胞特性，增强肿瘤发生能力，成为肿瘤学中潜在的新型治疗靶点。药用真菌安络小皮伞是一种具有多种生物学功能的中药，包括抗炎、抗氧化和抗癌作用。然而，安络小皮伞对 CSC 的抑制作用尚不清楚。
本研究旨在利用我们的治疗药物和人类全基因组 miRNA 筛选试剂盒，研究安络小皮伞菌丝体和提取物对源自各种人类癌细胞系的 CSC 的抑制作用。
本研究中，我们使用了多种人类癌细胞系，包括急性单核细胞白血病（THP-1）、多形性成胶质细胞瘤（GBM 8401）、肺腺癌（A549）、乳腺腺癌（MDA-MB-231）、肝癌（HepG2）、结直肠癌（SW620）和包皮成纤维细胞（HS68）。通过流式细胞术对细胞系生成的 CD133 CSC 进行了特征和分离，通过 MTT 测定评估了化疗和放疗的效果，同时通过 RT-PCR 和人类全基因组 qRT-PCR 确定了差异基因表达模式。还对安络小皮伞的抗癌作用与顺铂、紫杉醇或放疗进行了比较分析。
我们的结果表明，安络小皮伞菌丝体及其乙酸乙酯提取物对所有类型的 CSC 均具有增殖抑制作用，尤其是对肺癌、乳腺癌和头颈部鳞状细胞癌 CSC。此外，安络小皮伞联合放疗或化疗治疗 CSC 具有显著的抗癌效果。我们还发现，安络小皮伞的 CSC 抑制作用与脑和乳腺 CSC 中几种 microRNAs 的显著下调和癌症干细胞表达水平之间存在关联。更重要的是，CD133 表达水平较高与胶质母细胞瘤和乳腺癌患者的预后不良相关。
综上所述，我们证明了安络小皮伞作为一种有效的癌症治疗民族药理学治疗剂的潜力。
