title: Ascorbic acid and colon cancer: an oxidative stimulus to cell death depending on cell profile.
abstract: Colorectal cancer is a major health problem worldwide with urgent need for new and effective anti-cancer approaches that allow treating, increasing survival and improving life quality of patients. At pharmacological concentrations, ascorbic acid (AA) exerts a selective cytotoxic effect, whose mechanism of cytotoxicity remains unsolved. It has been suggested that it depends on the production of extracellular hydrogen peroxide, using ascorbate radical as an intermediate. The aim of this study was to evaluate the effects induced by AA in three colon cancer cell lines, as well as, possible cell death mechanisms involved. Our results showed that pharmacological concentrations of AA induce anti-proliferative, cytotoxic and genotoxic effects on three colon cancer cell lines under study. We also found that AA can induce cell death by an increment of oxidative stress, but also mediating a ROS-independent mechanism, as observed in LS1034 cells. This work explores AA anti-tumoral effects and highlights its applicability in the treatment of CC, underlying the importance of proceeding to clinical trials.
authors.affiliation: Biophysics Institute, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal; CIMAGO, FMUC-Faculty of Medicine, University of Coimbra, Portugal; CNC.IBILI, University of Coimbra, Portugal; Faculty of Sciences and Technology, University of Coimbra, Portugal. Electronic address: a.salome.pires@gmail.com.
authors.forename: Ana Salomé
authors.initials: AS
authors.lastname: Pires
authors.affiliation: Biophysics Institute, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal. Electronic address: claudiarfmarques@gmail.com.
authors.forename: Cláudia Raquel
authors.initials: CR
authors.lastname: Marques
authors.affiliation: Biophysics Institute, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal; CIMAGO, FMUC-Faculty of Medicine, University of Coimbra, Portugal. Electronic address: joaocrispim90@gmail.com.
authors.forename: João Carlos
authors.initials: JC
authors.lastname: Encarnação
authors.affiliation: Biophysics Institute, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal; CIMAGO, FMUC-Faculty of Medicine, University of Coimbra, Portugal; CNC.IBILI, University of Coimbra, Portugal. Electronic address: mabrantes@fmed.uc.pt.
authors.forename: Ana Margarida
authors.initials: AM
authors.lastname: Abrantes
authors.affiliation: Biophysics Institute, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal; CIMAGO, FMUC-Faculty of Medicine, University of Coimbra, Portugal; CNC.IBILI, University of Coimbra, Portugal; CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal. Electronic address: ana_mamede@hotmail.com.
authors.forename: Ana Catarina
authors.initials: AC
authors.lastname: Mamede
authors.affiliation: Biophysics Institute, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal; CIMAGO, FMUC-Faculty of Medicine, University of Coimbra, Portugal; CNC.IBILI, University of Coimbra, Portugal. Electronic address: mafaldalaranjo@gmail.com.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Laranjo
authors.affiliation: Biophysics Institute, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal; CIMAGO, FMUC-Faculty of Medicine, University of Coimbra, Portugal; Oncobiology and Hematology Laboratory, Applied Molecular Biology and University Clinic of Hematology, Faculty of Medicine, University of Coimbra, Portugal. Electronic address: acc.goncalves@gmail.com.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Gonçalves
authors.affiliation: Biophysics Institute, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal; CIMAGO, FMUC-Faculty of Medicine, University of Coimbra, Portugal; Oncobiology and Hematology Laboratory, Applied Molecular Biology and University Clinic of Hematology, Faculty of Medicine, University of Coimbra, Portugal; Centro Hospitalar Universitário de Coimbra, Hematology Department, Coimbra, Portugal. Electronic address: absarmento@fmed.uc.pt.
authors.forename: Ana Bela
authors.initials: AB
authors.lastname: Sarmento-Ribeiro
authors.affiliation: Biophysics Institute, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal; CIMAGO, FMUC-Faculty of Medicine, University of Coimbra, Portugal; CNC.IBILI, University of Coimbra, Portugal. Electronic address: mfbotelho@fmed.uc.pt.
authors.forename: Maria Filomena
authors.initials: MF
authors.lastname: Botelho
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D001205:Ascorbic Acid
keywords: Ascorbic acid; Cell death mechanisms; Colon cancer