Manabu Seino1, Masashi Okada2, Keita Shibuya3, Shizuka Seino4, Shuhei Suzuki5, Hiroyuki Takeda6, Tsuyoshi Ohta7, Hirohisa Kurachi8, Chifumi Kitanaka9. 1. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan. 2. 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. 3. 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. 4. 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. 5. 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. 6. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan. 7. Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan. 8. 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. 9. 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.
Abstract
BACKGROUND/AIM: 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. MATERIALS AND 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. CONCLUSION: 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. Copyright
BACKGROUND/AIM: 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. MATERIALS AND METHODS: The effects of resveratrol on the viability and self-renewal capacity of CSCs derived from A2780 humanovarian 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. CONCLUSION: 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. Copyright
Authors: James A McCubrey; Kvin Lertpiriyapong; Linda S Steelman; Steve L Abrams; Li V Yang; Ramiro M Murata; Pedro L Rosalen; Aurora Scalisi; Luca M Neri; Lucio Cocco; Stefano Ratti; Alberto M Martelli; Piotr Laidler; Joanna Dulińska-Litewka; Dariusz Rakus; Agnieszka Gizak; Paolo Lombardi; Ferdinando Nicoletti; Saverio Candido; Massimo Libra; Giuseppe Montalto; Melchiorre Cervello Journal: Aging (Albany NY) Date: 2017-06-12 Impact factor: 5.682