Research Divisions

Oxidative Stress

Group LeaderLocation and ContactMembersLines of ResearchNotable PublicationsProjectsPhD ThesesNews
Dra. Carmen Rodríguez
Professor Carmen Rodríguez

Carmen Rodríguez Sánchez

Carmen Rodriguez Sánchez studied Medicine at the Universidad de Oviedo, where she graduated in 1982. She obtained her PhD in 1989 in the Morphology and Cell Biology Department. She then completed a six-month postdoctoral fellowship (1989) at the University of Aberdeen in Scotland. From 1990 to 1991, she realised another postdoctoral fellowship, spending two years in the Cell and Structural Biology Department of the University of Texas Health Science Center at San Antonio (UTHSCSA) in the US. During this time, she worked in Dr Russel J. Reiter’s laboratory, where she began her research into the actions of melatonin and the intracellular signalling pathways regulated by this molecule. She then obtained a position as an Associate Lecturer in Human Anatomy, in the Morphology and Cell Biology Department of the Universidad de Oviedo. Subsequently, she completed two short postings in centres outside Spain: in 1992, she returned to the same laboratory in UTHSCSA for two months; and in 1994, she spent four months in Mary Imogene Bassett Hospital in New York. In the latter centre, she expanded the scope of her research into melatonin, studying the effects of this molecule on cancer. She is currently Professor of Human Anatomy and Embryology in the Morphology and Cell Biology Department of the Universidad de Oviedo. Since she began working at the Universidad de Oviedo, she has combined teaching – both of anatomy and doctoral-level courses – with the development of her research career, investigating the role of oxidative stress and antioxidants (such as melatonin) in cancer treatment. She is a member of the Instituto Universitario de Oncología del Principado de Asturias (IUOPA) and ISPA, where she is Principal Investigator of the Oxidative Stress Research Group.

Since 1995, the group she leads has made a substantial contribution to developing understanding about the action of melatonin, particularly: its ability to regulate the genetic expression (ALA-S, antioxidant enzymes); its cytoprotective action in healthy cells and tissue (this work being performed primarily in the nervous system); and its antitumour action. In recent years, the group’s work has focused on investigating intracellular signalling pathways regulated by melatonin in tumour cells (both stromal tumour cells and cancer stem cells); and on identifying differences in the tumour biology of different types of cancer which may be responsible for the distinct effects (anti-proliferative versus cytotoxic effects) that antioxidants, particularly melatonin, have upon these tumours. In parallel to this work, the group is exploring the intracellular redox state, as this seems to be key in explaining the differential action of this and other types of molecule according to the type of tumour. The group is also conducting studies on combining melatonin with other antitumour drugs that have synergistic effects, be these molecules in routine use or new generation molecules.

Carmen Rodriguez Sánchez’s research has been funded by the Spanish National R & D Plan (Ministry of Science and Instituto de Salud Carlos III) and the Regional R & D Plan (through FICYT: Foundation for the Promotion of Applied Scientific Research and Technology in Asturias). She has worked as principal investigator in research projects on a continuous basis since 1995.

Departamento de Morfología y Biología Celular.

Área de Anatomía, Facultad de Medicina,

Julián Clavería s/n, 33006 Oviedo, Spain

Telephone: +34 985103057

E-mail: carro@uniovi.es

Name Organisation Activity Euraxess classification
Álvarez Vega, Marco Antonio SESPA Research/Clinical/Teaching R2
Antolín González, Isaac Universidad de Oviedo Research/Teaching R3
Martín Fernández, Vanesa Universidad de Oviedo Research/Teaching R3
Rodríguez Sánchez, Carmen Universidad de Oviedo Research/Teaching R3
Sánchez Sánchez, Ana María Universidad de Oviedo Research/Teaching R2
Turos Cabal, María Universidad de Oviedo Research R1


Our group studies the antitumour properties of antioxidants and new synthetic compounds. We investigate their antitumour capacity when administered individually, as well as their ability to increase the efficacy of conventional chemotherapy. We also study the signalling pathways that mediate these effects, searching for new approaches by which to combine them with other antitumour molecules and/or use them on specific tumours, administering them in a targeted manner. In addition to the classic pathways activated after the receptor tyrosine kinases (MAPK, PI3K / Akt, etc.) or the death receptors have been activated, we are particularly interested in exploring the cell redox state and the interdependence between both pathways and cancer cell metabolism, as the latter’s role in the initiation and progression of cancer is well established. These studies are performed on commercially available tumour cell lines, tumour cells from patients – both cancer stem cells and stromal tumour cells – and experimental animal models.

We are currently focused on the following specific lines of research:

  1. Studying the cytotoxic action of the natural indoleamine melatonin and of new kinase inhibitors in Ewing sarcomas and haematological malignancies: we are characterising the intracellular signalling pathways used by these compounds when inducing cell death (apoptosis) in said tumours. These studies are being conducted on commercial cell lines and patient cells. The studies are also performed by inducing tumours in vivo, through the administration of luciferase-transfected tumour cells in NOD / SCID immunosuppressed mice, for monitoring with the In Vivo Image System (IVIS).
  2. Evaluation of the antitumour action of melatonin and new kinase inhibitors in human glioblastoma stem cells and stromal cells. We are also studying the signalling pathways used as part of the cytotoxic / anti-proliferative effect of these substances. The studies are performed on cancer stem cells obtained from patients via the Tumour Bank and on commercial cell lines such as stromal cells from complete tumours. In vivo experiments are conducted by implanting human glioblastoma stem cells into the brains of Balb / c-nu nude mice. This model provides a faithful replication of the patient’s tumour in the mouse, in contrast to experimental models in which stromal tumour cells are or commercial cell lines are implanted. In vivo monitoring of the tumour is performed using magnetic resonance imaging (MRI).
  3. Studying the antitumour efficacy of combinations of these substances with conventional chemotherapy. These studies are of particular interest when it comes to combining conventional or new combination chemotherapies with melatonin (which has negligible or no side effects). Melatonin has been shown to decrease the expression of the ABCG2 drug transporter in human glioblastomas, both in stromal tumour cells and cancer stem cells, which reduces the DL50 of the chemotherapeutics studied for both cell groups.
  4. Studying the differences in the tumour biology of various types of cancer, particularly in terms of basal metabolism and redox state, and their modification after the administration of melatonin and other antioxidant molecules. Several natural compounds known conventionally as antioxidants (such as resveratrol and melatonin) display different antitumour effects depending on the type of cancer: in most cases, they inhibit cell proliferation, while in some cases, they cause an early increase in intracellular oxidants and cell death. The specific objectives of these studies are: a) to gain information of what the target and the key points regarding the cytotoxic action of these compounds may be, according to the metabolic differences between the groups of tumours; b) to predict which types of tumours are sensitive to the different effects of these substances, classifying groups of tumours according to how they respond when this target is met; c) to establish a rationale for combining melatonin and other antioxidants with little or no side effects with other antitumour drugs that are already in use, so as to reduce the dosage, and thereby the adverse effects, of the latter; d) to advance our understanding of tumour metabolism and the use of new drugs that act on new therapeutic targets related to said metabolism.
  • Puente-Moncada N, Costales P, Antolín I, Nuñez LE, Oro P, Hermosilla M, Pérez-Escudero J, Ríos-Lombardía N, Sánchez-Sánchez AM, Luño E, Rodriguez C, Martín V y Morís F. The multikinase inhibitor EC70124 display potent activity in preclinical models of acute mieloid leukemia. Mol Cancer Ther 2018, 17:614-624.
  • Rodriguez-Blanco J, Pednekar L, Penas C, Li B, Martin V, Long J, Lee E, Weiss WA, Rodriguez C, Mehrdad N, Nguyen D, Ayad N, Rai P, Capobianco AJ, Robbins DJ. WNT signaling drives SHH-subgroup medulloblastoma growth. Oncogene 2017, 36:6306-6314
  • Letra-Vilela R, Sánchez-Sánchez AM, Rocha AM, Martin V, Branco-Santos J, Puente-Moncada N, Santa-Marta M, Outeiro TF, Antolín I, Rodriguez C, Herrera F. Distinct roles of N-acetyl and 5-methoxy groups in the antiproliferative and neuroprotective effects of melatonin. Mol Cell Endocrinol 2016, 434:238-49.
  • Sánchez-Sánchez AM, Antolín I, Puente-Moncada N, Suárez S, Gómez-Lobo M, Rodriguez C, Martín V. Melatonin cytotoxicity is associated to Warburg effect inhibition in Ewing’s sarcoma cells. Plos One. 2015, 10:e0135420.
  • Martín V, Herrera F, Sanchez-Sanchez AM, Puente-Moncada N, Gomez-Lobo M, Antolín I, Rodriguez C. Involvement of autophagiy in melatonin-induced cytotoxicity in glioma initiating cells. J. Pineal Res. 2014, 57:308-316.
  • Rodriguez C, Martín V, Herrera F, García-Santos G, Rodriguez-Blanco J, Casado-Zapico S, Sanchez-Sanchez AM, Suárez S, Puente-Moncada N, Anítua MJ and Antolín I. Mechanisms involved in the pro-apoptotic effect of melatonin in cancer cells. Int. J. Mol. Sci. 2013, 14:6597-6613.
  • Martín V, Sanchez-Sanchez A, Herrera García F, Gomez-Manzano C, Fueyo J, Alvarez Vega MA, Antolín I and Rodriguez C. Melatonin-induced methylation of the ABCG2/BCRP promoter as a novel mechanism to overcome multidrug resistance in brain tumor stem cells. Br. J. Cancer 2013, 108:2005-2012.
  • Rodriguez-Blanco J; Martin V; Garcia-Santos G; Herrera F; Casado-Zapico S; Antolin I; Rodríguez C. Cooperative action of JNK and Akt/mTOR in MPP+ induced autophagy of neuronal PC12 cells. J Neurosci Res 2012, 90:1850-1860.
  • Garcia-Santos G; Martin V; Rodriguez-Blanco J; Herrera F; Casado-Zapico S; Sánchez-Sánchez AM, AntolinI; Rodríguez C. Fas/Fas ligand regulation mediates cell death in human Ewing’s sarcoma cells treated with melatonin. Br J Cancer 2012, 106:1288-1296.
  • Casado-Zapico S, Martín V, García-Santos G, Rodríguez-Blanco J, Sánchez-Sánchez AM, Luño E, Suárez C, Garcí-Pedrero JM, Tirados-Menéndez S, Antolín I and Rodriguez C. Regulation of the expression of death receptors and their ligands by melatonin in haematological cancer cell lines and in leukaemia cells from patients. J Pineal Res 2011, 50:345-355.
  • Casado-Zapico S, García-Santos G, Rodriguez-Blanco J, Martin V, Antolín I, Medina M, Sánchez-Sánchez A y Rodriguez C. Synergistic antitumor effect of melatonin with several chemotherapeutic drugs on human Ewing sarcoma cancer cells: potentiation of the extrinsic apoptotic pathway. J Pineal Res 2010, 48:72-80.
  • Martin V, García-Santos G, Rodriguez-Blanco J, Casado-Zapico S, Sánchez-Sánchez A, Antolín I, Medina M y Rodriguez C. Melatonin sensitizes human malignant glioma cells against TRAIL-induced cell death. Cancer Lett 2010, 287:216-223.
  • Rodriguez-Blanco J, Martin V, Herrera F, García-Santos G, Antolín I y Rodriguez C. Intracellular signaling pathways involved in postmitotic dopaminergic PC12 cell death induced by 6-hydroxydopamine. J Neurochem 2008, 107:127-140.
  • Martin V, Herrera F, García-Santos G, Antolín I, Rodriguez-Blanco J, Medina M, Rodriguez C. Involvement of Protein kinase C in melatonin’s oncostatic effect in C6 glioma cells. J Pineal Res 2007, 43:239-244.
  • Carrera MP, Antolín I, Martin V, Sainz RM, Mayo JC, Herrera F, García-Santos G, Rodriguez C. Antioxidants do not prevent acrylonitrile-induced toxicity. Toxicol Lett. 2007, 169:236-244.
  • Martin V, Herrera F, García-Santos G, Antolín I, Rodriguez-Blanco J, Rodriguez C. Signaling pathways involved in antioxidant control of glioma cell proliferation. Free Radic Biol Med 2007, 42:1715-1722.
  • Herrera F, Martin V, García-Santos G, Rodriguez-Blanco J, Antolín I, Rodriguez C. Melatonin prevents glutamate-induced oxytosis in the HT22 mouse hippocampal cell line through an antioxidant effect specifically targeting mitochondria. J Neurochem. 2007, 100:736-746.
  • García-Santos G, Antolín I, Herrera F, Martín V, Rodríguez-Blanco J, Carrera MP, Rodríguez C. Melatonin induces apoptosis in human neuroblastona cancer cells. J Pineal Res 2006, 41:130-135.
  • Martín V, Herrera F, Carrera-González P, García Santos G, Antolin I, Rodriguez-Blanco J and Rodríguez C. Intracellular signaling pathways involved in the cell growth inhibition of glioma cells by melatonin. Cancer Res 2006, 66:1-8.
  • Herrera F, Martín V, Rodriguez-Blanco J, García-Santos G, Antolín I and Rodríguez C. Intracellular redox state regulation by parthenolide. Biochem Biophys Res Com 2005, 332:321-325.
  • Herrera F, Mayo JC, Martín V, Sainz RM, Antolín I and Rodríguez C. Apoptosis in primary lymphoid organs with aging. Cancer Lett 2004, 211:47-55.
  • Rodríguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martín V and Reiter RJ. Title: Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 2004, 36:1-9.
  • Antolin I, Rodriguez C, Sainz RM, Uría H, Mayo JC, Kotler ML, Rodriguez-Colunga MJ, Tolivia D y Menendez-Pelaez A. Neurohormone melatonin prevents cell damage: Effect on gene expression for antioxidant enzymes. FASEB Journal 1996, 10:882-890.

 

Principal Investigator Title Funding Body and Reference Number Duration Researchers
Carmen Rodríguez Sánchez Support for the activity of research groups conducting their work in Asturias Gobierno del Principado de Asturias: FICYT (GRUPIN14-081) 31/12/2014-31/12/2017 €90,000
Carmen Rodríguez Sánchez Tumour metabolism and miRNA regulation as determinants of the various antitumour effects of melatonin MINECO (SAF2014-58468-R) 01/01/2015-31/03/2018 €120,000
Carmen Rodríguez Sánchez Setting the dosage and efficacy studies of indolocarbazole EC-70124 in predictive animal models (INDOLKIN) MINECO (RTC-2016-4603-1)
With the participation of Entrechem SA and the Universidad de Oviedo
25/01/2016-31/06/2019 €160,000
Supervisors Title PhD Student Date Centre Honours
Carmen Rodríguez SánchezVanesa Martín Fernández Effects of melatonin on the glycolytic metabolism of tumour cells Ana María Sánchez Sánchez May 2014 Faculty of Medicine, Universidad de Oviedo Outstanding PhD award

Quality-assured PhD programme (ANECA)

International honours

Marco Antonio Alvarez Vega Prognostic factors in high-grade gliomas Sayoa Alvarez de Eulate Beramendi October 2016 Faculty of Medicine, Universidad de Oviedo
Marco Antonio Alvarez VegaSerafín Costilla García Endovascular treatment of acute ischaemic strokes using the Solitaire device Pedro Vega Valdés May 2017 Faculty of Medicine, Universidad de Oviedo
Carmen Rodríguez SánchezVanesa Martín Fernández Enhancing conventional and new combination chemotherapies with melatonin in acute myeloid leukaemia. Noelia Puente Moncada July 2018 Faculty of Medicine, Universidad de Oviedo Nominated for the outstanding PhD award

Quality-assured PhD programme (ANECA)

International honours