title: High-throughput screening identifies artesunate as selective inhibitor of cancer stemness: Involvement of mitochondrial metabolism.
abstract: Cancer stem cells (CSCs) have robust systems to maintain cancer stemness and drug resistance. Thus, targeting such robust systems instead of focusing on individual signaling pathways should be the approach allowing the identification of selective CSC inhibitors. Here, we used the alkaline phosphatase (ALP) assay to identify inhibitors for cancer stemness in induced cancer stem-like (iCSCL) cells. We screened several compounds from natural product chemical library and evaluated hit compounds for their efficacy on cancer stemness in iCSCL tumorspheres. We identified artesunate, an antimalarial drug, as a selective inhibitor of cancer stemness. Artesunate induced mitochondrial dysfunction that selectively inhibited cancer stemness of iCSCL cells, indicating an essential role of mitochondrial metabolism in cancer stemness.
authors.affiliation: Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan; Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan.
authors.forename: Amit
authors.initials: A
authors.lastname: Subedi
authors.affiliation: Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Futamura
authors.affiliation: Department of Microbiology, Yokohama City University School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Nishi
authors.affiliation: Department of Microbiology, Yokohama City University School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Ryo
authors.affiliation: Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan; Bio-Active Compounds Discovery Research Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan.
authors.forename: Nobumoto
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan; Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan. Electronic address: hisyo@riken.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000008:administration & dosage*; D000077332:Artesunate; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; D024101:Mitochondrial Proteins; D000077332:Artesunate
keywords: Artesunate; CSCs; High-throughput screening; Mitochondrial metabolism; Tumorspheres