title: Glutathione in metastases: From mechanisms to clinical applications.
abstract: Metastatic spread, not primary tumors, is the leading cause of cancer death. Glutathione (γ-glutamyl-cysteinyl-glycine, GSH) is particularly relevant in cancer cells as it is involved in regulating carcinogenic mechanisms, growth and dissemination, and multidrug and radiation resistance. Upon interaction of metastatic cells with the vascular endothelium, a high percentage of metastatic cells with high GSH levels survive the combined nitrosative and oxidative stresses elicited by the vascular endothelium. GSH release from different organs, mainly the liver, and its interorgan transport through the blood circulation to metastatic foci, promote their growth. This review focuses on the relationship among GSH and different key mechanisms that facilitate metastatic cell survival and growth, i.e. adaptive responses to stress, cell death evasion and utilization of physiological neuroendocrine mechanisms. Different strategies that are aimed at sensitizing metastases to cancer therapy by depleting metastatic cell GSH are analyzed.
authors.affiliation: a Department of Physiology , Faculty of Medicine and Odontology and.|b Department of Physiology , Faculty of Pharmacy, University of Valencia , Valencia , Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Estrela
authors.affiliation: b Department of Physiology , Faculty of Pharmacy, University of Valencia , Valencia , Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Ortega
authors.affiliation: b Department of Physiology , Faculty of Pharmacy, University of Valencia , Valencia , Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Mena
authors.affiliation: b Department of Physiology , Faculty of Pharmacy, University of Valencia , Valencia , Spain.
authors.forename: J Antoni
authors.initials: JA
authors.lastname: Sirerol
authors.affiliation: a Department of Physiology , Faculty of Medicine and Odontology and.
authors.forename: Elena
authors.initials: E
authors.lastname: Obrador
mesh_terms: D000818:Animals; D005978:Glutathione / Q000378:metabolism / Q000502:physiology; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism / Q000503:physiopathology
chemical_list: D005978:Glutathione
keywords: Glutathione; cancer; metastases; neuroendocrine regulation; oncotherapy; stress