title: Cellular acidification as a new approach to cancer treatment and to the understanding and therapeutics of neurodegenerative diseases.
abstract: During the last few years, the understanding of the dysregulated hydrogen ion dynamics and reversed proton gradient of cancer cells has resulted in a new and integral pH-centric paradigm in oncology, a translational model embracing from cancer etiopathogenesis to treatment. The abnormalities of intracellular alkalinization along with extracellular acidification of all types of solid tumors and leukemic cells have never been described in any other disease and now appear to be a specific hallmark of malignancy. As a consequence of this intracellular acid-base homeostatic failure, the attempt to induce cellular acidification using proton transport inhibitors and other intracellular acidifiers of different origins is becoming a new therapeutic concept and selective target of cancer treatment, both as a metabolic mediator of apoptosis and in the overcoming of multiple drug resistance (MDR). Importantly, there is increasing data showing that different ion channels contribute to mediate significant aspects of cancer pH regulation and etiopathogenesis. Finally, we discuss the extension of this new pH-centric oncological paradigm into the opposite metabolic and homeostatic acid-base situation found in human neurodegenerative diseases (HNDDs), which opens novel concepts in the prevention and treatment of HNDDs through the utilization of a cohort of neural and non-neural derived hormones and human growth factors.
authors.affiliation: Institute of Clinical Biology and Metabolism, c) Postas 13, 01004 Vitoria, Spain. Electronic address: salvaszh@telefonica.net.
authors.forename: Salvador
authors.initials: S
authors.lastname: Harguindey
authors.affiliation: Institute of Clinical Biology and Metabolism, c) Postas 13, 01004 Vitoria, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Stanciu
authors.affiliation: Department of Physiology, School of Medicine, University of Santiago de Compostela, Spain and Scientific Director of Foltra Medical Centre, Teo, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Devesa
authors.affiliation: Al-Ghad International Colleges for Applied Medical Sciences, Al-Madinah Al-Munawarah, Saudi Arabia.
authors.forename: Khalid
authors.initials: K
authors.lastname: Alfarouk
authors.affiliation: Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Via E. Orabona 4, 70125 Bari, Italy.
authors.forename: Rosa Angela
authors.initials: RA
authors.lastname: Cardone
authors.affiliation: Institute of Clinical Biology and Metabolism, c) Postas 13, 01004 Vitoria, Spain.
authors.forename: Julian David
authors.initials: JD
authors.lastname: Polo Orozco
authors.affiliation: Research and Development, Medical Centre Foltra, Teo, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Devesa
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham,College Road, Sutton Bonington, LE12 5RD, UK.
authors.forename: Cyril
authors.initials: C
authors.lastname: Rauch
authors.affiliation: Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country, Networking Biomedical Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, SLFPB-EHU, 01006 Vitoria, Spain.
authors.forename: Gorka
authors.initials: G
authors.lastname: Orive
authors.affiliation: BTI Biotechnology Institute ImasD, S.L. C/Jacinto Quincoces, 39, 01007 Vitoria, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Anitua
authors.affiliation: Inserm UMR1069, University François-Rabelais of Tours,10 Boulevard Tonnellé, 37032 Tours, France; Institut Universitaire de France, 1 Rue Descartes, Paris 75231, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Roger
authors.affiliation: Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Via E. Orabona 4, 70125 Bari, Italy.
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Reshkin
mesh_terms: D000143:Acids / Q000378:metabolism*; D017209:Apoptosis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000628:therapy*
chemical_list: D000143:Acids
keywords: Cellular acidification in cancer treatment; Cellular acidifiers; Growth factors in cancer and neurodegenerative diseases; Ion channels in cancer and neurodegeneration; pH, NHE, cancer and neurodegenerative diseases