GK-1 Induces Oxidative Stress, Mitochondrial Dysfunction, Decreased Membrane Potential, and Impaired Autophagy Flux in a Mouse Model of Breast Cancer

Cruz-Gregorio, Alfredo and Aranda-Rivera, Ana Karina and Aparicio-Trejo, Omar Emiliano and Medina-Campos, Omar Noel and Sciutto, Edda and Fragoso, Gladis and Pedraza-Chaverri, José (2022) GK-1 Induces Oxidative Stress, Mitochondrial Dysfunction, Decreased Membrane Potential, and Impaired Autophagy Flux in a Mouse Model of Breast Cancer. Antioxidants, 12 (1). p. 56. ISSN 2076-3921

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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.

Item Type: Article
Subjects: GO for STM > Agricultural and Food Science
Depositing User: Unnamed user with email support@goforstm.com
Date Deposited: 15 Dec 2023 12:40
Last Modified: 15 Dec 2023 12:40
URI: http://archive.article4submit.com/id/eprint/2531

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