Iron cycle disruption by heme oxygenase-1 activation leads to a reduced breast cancer cell survival.

Autor: Giorgi G; Laboratorio de Fisiología Humana, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS), 8000 Bahía Blanca, Argentina., Mascaró M; Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Universidad Nacional del Sur (UNS)-CONICET, Departamento de Biología, Bioquímica y Farmacia (UNS), 8000 Bahía Blanca, Argentina., Gandini NA; Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Universidad Nacional del Sur (UNS)-CONICET, Departamento de Biología, Bioquímica y Farmacia (UNS), 8000 Bahía Blanca, Argentina., Rabassa ME; Centro de Investigaciones Inmunológicas Básicas y Aplicadas (CINIBA), Facultad de Ciencias Médicas, Universidad Nacional de La Plata (UNLP), 1900 La Plata, Buenos Aires, Argentina., Coló GP; Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Universidad Nacional del Sur (UNS)-CONICET, Departamento de Biología, Bioquímica y Farmacia (UNS), 8000 Bahía Blanca, Argentina., Arévalo J; Servicio de Patología, Hospital Interzonal de Agudos 'Dr. José Penna', 8000 Bahía Blanca, Argentina., Curino AC; Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Universidad Nacional del Sur (UNS)-CONICET, Departamento de Biología, Bioquímica y Farmacia (UNS), 8000 Bahía Blanca, Argentina. Electronic address: acurino@criba.edu.ar., Facchinetti MM; Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Universidad Nacional del Sur (UNS)-CONICET, Departamento de Biología, Bioquímica y Farmacia (UNS), 8000 Bahía Blanca, Argentina., Roque ME; Laboratorio de Fisiología Humana, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS), 8000 Bahía Blanca, Argentina.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2023 Mar; Vol. 1869 (3), pp. 166621. Date of Electronic Publication: 2022 Dec 17.
DOI: 10.1016/j.bbadis.2022.166621
Abstrakt: Heme oxygenase-1 (HO-1), which catalyzes heme degradation releasing iron, regulates several processes related to breast cancer. Iron metabolism deregulation is also connected with several tumor processes. However the regulatory relationship between HO-1 and iron proteins in breast cancer remains unclear. Using human breast cancer biopsies, we found that high HO-1 levels significantly correlated with low DMT1 levels. Contrariwise, high HO-1 levels significantly correlated with high ZIP14 and prohepcidin expression, as well as hemosiderin storage. At mRNA level, we found that high HO-1 expression significantly correlated with low DMT1 expression but high ZIP14, L-ferritin and hepcidin expression. In in vivo experiments in mice with genetic overexpression or pharmacological activation of HO-1, we detected the same expression pattern observed in human biopsies. In in vitro experiments, HO-1 activation induced changes in iron proteins expression leading to an increase of hemosiderin, ROS levels, lipid peroxidation and a decrease of the growth rate. Such low growth rate induced by HO-1 activation was reversed when iron levels or ROS levels were reduced. Our findings demonstrate an important role of HO-1 on iron homeostasis in breast cancer. The changes in iron proteins expression when HO-1 is modulated led to the iron accumulation deregulating the iron cell cycle, and consequently, generating oxidative stress and low viability, all contributing to impair breast cancer progression.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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