<i>Antrodia cinnamomea</i> Enhances Chemo-Sensitivity of 5-FU and Suppresses Colon Tumorigenesis and Cancer Stemness via Up-Regulation of Tumor Suppressor miR-142-3p

• Main Authors: Yan-Jiun Huang, Vijesh Kumar Yadav, Prateeti Srivastava, Alexander TH Wu, Thanh-Tuan Huynh, Po-Li Wei, Chi-Ying F. Huang, Tse-Hung Huang
• Format: Article
• Language: English
• Published: MDPI AG 2019-07-01
• Series: Biomolecules
• Subjects: colon cancer; <i>AC</i>; 5-FU; EMT; stemness; miR-142-3p
• Online Access: https://www.mdpi.com/2218-273X/9/8/306

5-Fluorouracil (5-FU) regimen remains the backbone of the first-line agent to treat colon cancer, but often these patients develop resistance. Cancer stem cells (CSC&#8217;s) are considered as one of the key contributors in the development of drug resistance and tumor recurrence. We aimed to provide preclinical evidence for <i>Antrodia cinnamomea</i> (<i>AC</i>), as a potential in suppressing colon cancer CSC&#8217;s to overcome 5-FU drug-resistant. In-vitro assays including cell viability, colony formation, <i>AC</i> + 5-FU drug combination index and tumor sphere generation were applied to determine the inhibitory effect of <i>AC</i>. Mouse xenograft models also incorporated to evaluate in vivo effect of <i>AC</i>. <i>AC</i> treatment significantly inhibited the proliferation, colony formation and tumor sphere generation. <i>AC</i> also inhibited the expression of oncogenic markers (NF-&#954;B, and C-myc), EMT/metastasis markers (vimentin and MMP3) and stemness associated markers (&#946;-catenin, SOX-2 and Nanog). Sequential treatment of <i>AC</i> and 5-FU synergized and reduces colon cancer viability both in vivo and in vitro. Mechanistically, <i>AC</i> mediated anti-tumor effect was associated with an increased level of tumor suppressor microRNAs especially, miR142-3p. <i>AC</i> can be a potent synergistic adjuvant, down-regulates cancer stemness genes and enhances the antitumor ability of 5-FU by stimulating apoptosis-associated genes, suppressing inflammation and metastasis genes through miR142-3p in colon cancer.