title: Andrographolide impedes cancer stemness and enhances radio-sensitivity in oral carcinomas via miR-218 activation.
abstract: Current evidence suggests that oral cancer stem cells (OCSCs) possess high tumorigenic and metastatic properties as well as chemo- and radioresistance. In this study, we demonstrated that andrographolide, the main bioactive component in the medicinal plant Andrographis, significantly reduced oncogenicity and restored radio-sensitivity of ALDH1+CD44+ OCSCs. Mechanistic studies showed that andrographolide treatment increased the expression of microRNA-218 (miR-218), leading to the downregulation of Bmi1. We showed that knockdown of miR-218 in ALDH1-CD44- non-OCSCs enhanced cancer stemness, while silencing of Bmi1 significantly counteracted it. Furthermore, we found tumor growth was reduced in mice bearing xenograft tumors after andrographolide treatment via activation of miR-218/Bmi1 axis. Together, these data demonstrated that the inhibition of tumor aggressiveness in OCSCs by andrographolide was mediated through the upregulation of miR-218, thereby reducing Bmi1 expression. These findings suggest that andrographolide may be a valuable natural compound for anti-CSCs treatment of OSCC.
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.|Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.|Oral Medicine Center, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Po-Yu
authors.initials: PY
authors.lastname: Yang
authors.affiliation: Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Pei-Ling
authors.initials: PL
authors.lastname: Hsieh
authors.affiliation: Tissue Bank, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.|Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan.|Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan.
authors.forename: Tong Hong
authors.initials: TH
authors.lastname: Wang
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.|Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.|Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan.|Oral Medicine Center, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Cheng-Chia
authors.initials: CC
authors.lastname: Yu
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.|Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.|Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan.|Oral Medicine Center, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Lu
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Liao
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.|Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Tzu-Hsin
authors.initials: TH
authors.lastname: Lee
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.|Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.|Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan.|Oral Medicine Center, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Peng
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004224:Diterpenes / Q000008:administration & dosage* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009062:Mouth Neoplasms / Q000235:genetics / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D063150:Polycomb Repressive Complex 1 / Q000235:genetics; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C069077:BMI1 protein, human; D004224:Diterpenes; C547471:MIRN218 microRNA, human; D035683:MicroRNAs; D011838:Radiation-Sensitizing Agents; C030419:andrographolide; D063150:Polycomb Repressive Complex 1
keywords: andrographolide; cancer stemness; miR-218; oral squamous cell carcinomas