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Small Molecule MIF Modulation Enhances Ferroptosis by Impairing DNA Repair Mechanisms.
Chen, Deng; Zhao, Chunlong; Zhang, Jianqiu; Knol, Catharina W J; Osipyan, Angelina; Majerníková, Nad'a; Chen, Tingting; Xiao, Zhangping; Adriana, Jeaunice; Griffith, Andrew J; Gamez, Abel Soto; van der Wouden, Petra E; Coppes, Robert P; Dolga, Amalia M; Haisma, Hidde J; Dekker, Frank J.
Afiliación
  • Chen D; Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, The Netherlands.
  • Zhao C; Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, The Netherlands.
  • Zhang J; Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, The Netherlands.
  • Knol CWJ; Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, The Netherlands.
  • Osipyan A; Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, The Netherlands.
  • Majerníková N; Research School of Behavioural and Cognitive Neuroscience, University of Groningen, Groningen, 9713 AV, The Netherlands.
  • Chen T; Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands.
  • Xiao Z; Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, 9713 AV, The Netherlands.
  • Adriana J; Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, 9713 AV, The Netherlands.
  • Griffith AJ; Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, The Netherlands.
  • Gamez AS; Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, The Netherlands.
  • van der Wouden PE; Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, The Netherlands.
  • Coppes RP; Department of Biomedical Sciences of Cell & Systems, Section Molecular Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, 9712 CP, The Netherlands.
  • Dolga AM; Department of Radiation Oncology, University Medical Center Groningen, Hanzeplein 1, Groningen, 9713 GZ, Netherlands.
  • Haisma HJ; Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, The Netherlands.
  • Dekker FJ; Department of Biomedical Sciences of Cell & Systems, Section Molecular Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, 9712 CP, The Netherlands.
Adv Sci (Weinh) ; 11(32): e2403963, 2024 Aug.
Article en En | MEDLINE | ID: mdl-38924362
ABSTRACT
Ferroptosis is a form of regulated cell death that can be modulated by small molecules and has the potential for the development of therapeutics for oncology. Although excessive lipid peroxidation is the defining hallmark of ferroptosis, DNA damage may also play a significant role. In this study, a potential mechanistic role for MIF in homologous recombination (HR) DNA repair is identified. The inhibition or genetic depletion of MIF or other HR proteins, such as breast cancer type 1 susceptibility protein (BRCA1), is demonstrated to significantly enhance the sensitivity of cells to ferroptosis. The interference with HR results in the translocation of the tumor suppressor protein p53 to the mitochondria, which in turn stimulates the production of reactive oxygen species. Taken together, the findings demonstrate that MIF-directed small molecules enhance ferroptosis via a putative MIF-BRCA1-RAD51 axis in HR, which causes resistance to ferroptosis. This suggests a potential novel druggable route to enhance ferroptosis by targeted anticancer therapeutics in the future.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores Inhibidores de la Migración de Macrófagos / Reparación del ADN / Ferroptosis Límite: Humans Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Alemania
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores Inhibidores de la Migración de Macrófagos / Reparación del ADN / Ferroptosis Límite: Humans Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Alemania