Yu-Kai Su1, Ping-Hsiao Shih2, Wei-Hwa Lee3, Oluwaseun Adebayo Bamodu4, Alexander T H Wu5, Chun-Chih Huang6, Yew-Min Tzeng6, Michael Hsiao7, Chi-Tai Yeh8, Chien-Min Lin9. 1. 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. 2. Department of Pediatrics, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. 3. Department of Pathology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan. 4. Cancer Center, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; Department of Medical Research & Education, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan. 5. The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. 6. Department of Life Science, National Taitung University, Taitung, Taiwan. 7. Genomics Research Center, Academia Sinica, Taipei, Taiwan. 8. Cancer Center, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; Department of Medical Research & Education, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan. Electronic address: ctyeh@s.tmu.edu.tw. 9. 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. Electronic address: m513092004@s.tmu.edu.tw.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Herein, we demonstrate the putative role of A. cinnamomea as an effective ethnopharmacologic therapeutic agent for cancer treatment.
ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: To investigate the inhibitory effect of A. cinnamomea mycelium and extract on CSCs derived from various humancancer cell lines using our in-house therapeutics and human genome-wide miRNA screening panels. MATERIALS AND METHODS: A broad range of humancancer 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. RESULTS: 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 cancerpatients. CONCLUSION: Herein, we demonstrate the putative role of A. cinnamomea as an effective ethnopharmacologic therapeutic agent for cancer treatment.
Authors: Sona Uramova; Peter Kubatka; Zuzana Dankova; Andrea Kapinova; Barbora Zolakova; Marek Samec; Pavol Zubor; Anthony Zulli; Vanda Valentova; Taeg Kyu Kwon; Peter Solar; Martin Kello; Karol Kajo; Dietrich Busselberg; Martin Pec; Jan Danko Journal: EPMA J Date: 2018-11-12 Impact factor: 6.543