title: Eucommicin A, a β-truxinate lignan from Eucommia ulmoides, is a selective inhibitor of cancer stem cells.
abstract: Cancer stem cells (CSCs) constitute a small population of undifferentiated cells within a tumor that have the ability to self-renew and drive tumor formation, thus behaving as cancer-initiating cancer cells. Therapeutic interventions that eliminate CSCs are necessary to completely cure patients, since CSCs are a crucial source of tumor recurrence and metastasis. An induced CSC-like (iCSCL) model was recently established using induced pluripotent stem cells (iPSCs). In this study, a natural product-eucommicin A-was identified from Eucommia ulmoides leaves by screening for anti-CSC activity using the iCSCL model. Its structure was elucidated by spectroscopic methods as a quinic acid diester of 3,4,3',4'-tetrahydroxy-β-truxinic acid. Eucommicin A exhibited selective anti-CSC activity and inhibited tumor sphere formation by iCSCL cells. The results of this study suggest that eucommicin A could serve as a lead compound in the development of drugs to abrogate the stemness and self-renewal ability of CSCs.
authors.affiliation: Department of Bioresource Science, Ibaraki University, Inashiki-gun, Ibaraki 300-0393, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Fujiwara
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: RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Department of Bioresource Science, Ibaraki University, Inashiki-gun, Ibaraki 300-0393, Japan.
authors.forename: Morifumi
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Hekizan-en Co., Ltd., Aiko-gun, Kanagawa 243-0307, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Yasuma
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: Department of Bioresource Science, Ibaraki University, Inashiki-gun, Ibaraki 300-0393, Japan. Electronic address: ayoshi@mx.ibaraki.ac.jp.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D031283:Eucommiaceae / Q000737:chemistry*; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D014411:Neoplastic Stem Cells / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D017705:Lignans; C000610925:eucommicin A
keywords: Cancer stem cell; Eucommia ulmoides; Eucommiaceae; Lignan; β-Truxinate