Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/3524
Title: Endothelin-1 as a Mediator of Heme Oxygenase-1-Induced Stemness in Colorectal Cancer: Influence of p53
Authors: Ríos-Arrabal, Sandra
Puentes-Pardo, Jose D.
Moreno-SanJuan, Sara
Szuba, Ágata
Casado, Jorge
García-Costela, María
Escudero-Feliu, Julia
Verbeni, Michela
Cano, Carlos
González-Puga, Cristina
Martín-Lagos Maldonado, Alicia
Carazo, Ángel
León, Josefa
metadata.dc.contributor.authoraffiliation: [Ríos-Arrabal,S; Puentes-Pardo,JD; Moreno-SanJuan,S; Casado,J; García-Costela,M; Escudero-Feliu,J; González-Puga,C; Martín-Lagos Maldonado,A; Carazo,A; León,J] Instituto de Investigación Biosanitaria de Granada, ibs.GRANADA, Granada, Spain. [Puentes-Pardo,JD] Departamento de Farmacología, Facultad de Farmacia, Universidad de Granada, Granada, Spain. [Moreno-SanJuan,S] Cytometry and Microscopy Research Service, Instituto de Investigación Biosanitaria de Granada, ibs.GRANADA, Granada, Spain. [Szuba,A] Unidad de Gestión Clínica de Cirugía, Complejo Hospitalario de Jaén, Jaén, Spain. [Verbeni,M; Cano,C] Departamento de Ciencias de la Computación e Inteligencia Artificial, E.T.S. de Ingenierías Informática y de Telecomunicación, Universidad de Granada, Granada, Spain. [González-Puga,C] Unidad de Gestión Clínica de Cirugía, Hospital Universitario San Cecilio de Granada, Granada, Spain. [Martín-Lagos Maldonado,A; León,J] Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario San Cecilio de Granada, Granada, Spain.
Keywords: Colorectal cancer;Cancer stem cells;Heme oxygenase-1;Endothelin-1;Endothelin converting enzyme-1;Bosentan;Neoplasias colorrectales;Hemo-oxigenasa 1;Endotelina-1;Bosentán
metadata.dc.subject.mesh: Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxygenases::Mixed Function Oxygenases::Heme Oxygenase (Decyclizing)::Heme Oxygenase-1
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Endothelins::Endothelin-1
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Protective Agents::Antioxidants
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms
Issue Date: 4-Jun-2021
Publisher: MDPI
Citation: Rios-Arrabal S, Puentes-Pardo JD, Moreno-SanJuan S, Szuba A, Casado J, Garcia-Costela M, et al. Endothelin-1 as a Mediator of Heme Oxygenase-1-Induced Stemness in Colorectal Cancer: Influence of p53. Journal of Personalized Medicine. 2021;11(6):509
Abstract: Heme oxygenase-1 (HO-1) is an antioxidant protein implicated in tumor progression, metastasis, and resistance to therapy. Elevated HO-1 expression is associated with stemness in several types of cancer, although this aspect has not yet been studied in colorectal cancer (CRC). Using an in vitro model, we demonstrated that HO-1 overexpression regulates stemness and resistance to 5-FU treatment, regardless of p53. In samples from CRC patients, HO-1 and endothelin converting enzyme-1 (ECE-1) expression correlated significantly, and p53 had no influence on this result. Carbon monoxide (CO) activated the ECE-1/endothelin-1 (ET-1) pathway, which could account for the protumoral effects of HO-1 in p53 wild-type cells, as demonstrated after treatment with bosentan (an antagonist of both ETRA and ETRB endothelin-1 receptors). Surprisingly, in cells with a non-active p53 or a mutated p53 with gain-of-function, ECE-1-produced ET-1 acted as a protective molecule, since treatment with bosentan led to increased efficiency for spheres formation and percentage of cancer stem cells (CSCs) markers. In these cells, HO-1 could activate or inactivate certain unknown routes that could induce these contrary responses after treatment with bosentan in our cell model. However more research is warranted to confirm these results. Patients carrying tumors with a high expression of both HO-1 and ECE-1 and a non-wild-type p53 should be considered for HO-1 based-therapies instead of ET-1 antagonists-based ones.
URI: http://hdl.handle.net/10668/3524
metadata.dc.relation.publisherversion: https://www.mdpi.com/2075-4426/11/6/509/htm
metadata.dc.identifier.doi: 10.3390/jpm11060509
ISSN: 2075-4426 (Online)
Appears in Collections:01- Artículos - Complejo Hospitalario de Jaén
01- Artículos - Hospital San Cecilio
01- Artículos - ibsGRANADA. Instituto de Investigación Biosanitaria de Granada

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