title: Differential contribution of ROS to resveratrol-induced cell death and loss of self-renewal capacity of ovarian cancer stem cells.
abstract: OBJECTIVE
  Cancer stem cells (CSCs) are considered to contribute to the poor prognosis of ovarian cancer as a major cause of fatal recurrence. Identification of effective measures to eliminate ovarian CSCs through induction of cell death and/or loss of self-renewal capacity would, therefore, be key to successful management of ovarian cancer.
  
  
  METHODS
  The effects of resveratrol on the viability and self-renewal capacity of CSCs derived from A2780 human ovarian cancer cells were examined. The involvement of reactive oxygen species (ROS) was also investigated.
  
  
  RESULTS
  At a non-toxic to normal human fibroblasts concentration, resveratrol effectively killed ovarian CSCs independently of ROS, while ROS-dependently impaired the self-renewal capacity of ovarian CSCs that survived resveratrol treatment.
  
  
  CONCLUSIONS
  Our findings not only shed light on a novel mechanism of action for resveratrol but also suggest that resveratrol, or its analogs, may be useful for CSC-directed therapy against ovarian cancer.
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Seino
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan Oncology Research Center, Research Institute for Advanced Molecular Epidemiology, Yamagata University, Yamagata, Japan Global COE program for Medical Sciences, Japan Society for Promotion of Science, Tokyo, Japan Research Institute for Promotion of Medical Sciences, Yamagata University School of Medicine, Yamagata, Japan Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan Department of Regional Cancer Network, Yamagata University School of Medicine, Yamagata, Japan Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Oncology Research Center, Research Institute for Advanced Molecular Epidemiology, Yamagata University, Yamagata, Japan Global COE program for Medical Sciences, Japan Society for Promotion of Science, Tokyo, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Shibuya
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Oncology Research Center, Research Institute for Advanced Molecular Epidemiology, Yamagata University, Yamagata, Japan Global COE program for Medical Sciences, Japan Society for Promotion of Science, Tokyo, Japan Research Institute for Promotion of Medical Sciences, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Seino
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan Department of Regional Cancer Network, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takeda
authors.affiliation: Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ohta
authors.affiliation: Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kurachi
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Oncology Research Center, Research Institute for Advanced Molecular Epidemiology, Yamagata University, Yamagata, Japan Global COE program for Medical Sciences, Japan Society for Promotion of Science, Tokyo, Japan Research Institute for Promotion of Medical Sciences, Yamagata University School of Medicine, Yamagata, Japan ckitanak@med.id.yamagata-u.ac.jp.
authors.forename: Chifumi
authors.initials: C
authors.lastname: Kitanaka
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000502:physiology*; D010051:Ovarian Neoplasms; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017382:Reactive Oxygen Species; D013267:Stilbenes; D000077185:Resveratrol
keywords: Cancer initiating cells; chemoprevention; ovarian cancer; oxidative stress