Cruz-Gregorio 2022 Antioxidants (Basel)

From Bioblast
Publications in the MiPMap
Cruz-Gregorio A, Aranda-Rivera AK, Aparicio-Trejo OE, Medina-Campos ON, Sciutto E, Fragoso G, Pedraza-Chaverri J (2022) GK-1 Induces oxidative stress, mitochondrial dysfunction, decreased membrane potential, and impaired autophagy flux in a mouse model of breast cancer.

Β» Antioxidants (Basel) 12:56. PMID: 36670920 Open Access

Cruz-Gregorio Alfredo, Aranda-Rivera Ana Karina, Aparicio-Trejo Omar Emiliano, Medina-Campos Omar Noel, Sciutto Edda, Fragoso Gladis, Pedraza-Chaverri Jose (2022) Antioxidants (Basel)

Abstract: Breast cancer (BC) is the second most common cancer worldwide in women. During the last decades, the mortality due to breast cancer has progressively decreased due to early diagnosis and the emergence of more effective new treatments. However, human epidermal growth factor receptor 2 (HER2) and triple-negative breast cancer (TNBC) remain with poor prognoses. In our research group, we are proposing the GK-1 immunomodulatory peptide as a new alternative for immunotherapy of these aggressive tumors. GK-1 reduced the growth rate of established tumors and effectively reduced lung metastasis in the 4T1 experimental murine model of breast cancer. Herein, the effect of GK-1 on the redox state, mitochondrial metabolism, and autophagy of triple-negative tumors that can be linked to cancer evolution was studied. GK-1 decreased catalase activity, reduced glutathione (GSH) content and GSH/oxidized glutathione (GSSG) ratio while increased hydrogen peroxide (H2O2) production, GSSG, and protein carbonyl content, inducing oxidative stress (OS) in tumoral tissues. This imbalance between reactive oxygen species (ROS) and antioxidants was related to mitochondrial dysfunction and uncoupling, characterized by reduced mitochondrial respiratory parameters and dissipation of mitochondrial membrane potential (ΔΨm), respectively. Furthermore, GK-1 likely affected autophagy flux, confirmed by elevated levels of p62, a marker of autophagy flux. Overall, the induction of OS, dysfunction, and uncoupling of the mitochondria and the reduction of autophagy could be molecular mechanisms that underlie the reduction of the 4T1 breast cancer induced by GK-1. β€’ Keywords: ATP synthase, GK-1, VDAC, Autophagy flux, Mitochondrial dysfunction, Oxidative stress β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: MX Mexico City Pedraza Chaverri J

Labels: MiParea: Respiration  Pathology: Cancer 

Organism: Mouse  Tissue;cell: Endothelial;epithelial;mesothelial cell  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS  Pathway: N, ROX  HRR: Oxygraph-2k, O2k-Fluorometer 

2023-01, AmR 

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