Cruz-Gregorio 2023 Phytother Res
Cruz-Gregorio A, Aranda-Rivera AK, Aparicio-Trejo OE, Medina-Campos ON, Sciutto E, Fragoso G, Pedraza-Chaverri J (2023) Ξ±-Mangostin induces oxidative damage, mitochondrial dysfunction, and apoptosis in a triple-negative breast cancer model. https://doi.org/10.1002/ptr.7812 |
Β» Phytother Res [Epub ahead of print]. PMID: 37012651 Open Access
Cruz-Gregorio Alfredo, Aranda-Rivera Ana Karina, Aparicio-Trejo Omar Emiliano, Medina-Campos Omar Noel, Sciutto Edda, Fragoso Gladis, Pedraza-Chaverri Jose (2023) Phytother Res
Abstract: Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor; therefore, TNBC lacks targeted therapy, and chemotherapy is the only available treatment for this illness but causes side effects. A putative strategy for the treatment of TNBC could be the use of the polyphenols such as Ξ±-Mangostin (Ξ±-M), which has shown anticancerogenic effects in different cancer models and can modulate the inflammatory and prooxidant state in several pathological models. The redox state, oxidative stress (OS), and oxidative damage are highly related to cancer development and its treatment. Thus, this study aimed to evaluate the effects of Ξ±-M on redox state, mitochondrial metabolism, and apoptosis in 4T1 mammary carcinoma cells. We found that Ξ±-M decreases both protein levels and enzymatic activity of catalase, and increases reactive oxygen species, oxidized proteins and glutathione disulfide, which demonstrates that Ξ±-M induces oxidative damage. We also found that Ξ±-M promotes mitochondrial dysfunction by abating basal respiration, the respiration ligated to oxidative phosphorylation (OXPHOS), and the rate control of whole 4T1 cells. Additionally, Ξ±-M also decreases the levels of OXPHOS subunits of mitochondrial complexes I, II, III, and adenosine triphosphate synthase, the activity of mitochondrial complex I as well as the levels of peroxisome proliferator-activated receptor-gamma co-activator 1Ξ±, showing a mitochondrial mass reduction. Then, oxidative damage and mitochondrial dysfunction induced by Ξ±-M induce apoptosis of 4T1 cells, which is evidenced by B cell lymphoma 2 decrease and caspase 3 cleavage. Taken together, our results suggest that Ξ±-M induces OS and mitochondrial dysfunction, resulting in 4T1 cell death through apoptotic mechanisms. β’ Keywords: 4T1 cells, Mitochondrial dysfunction, Oxidative stress, Triple-negative breast cancer (TNBC), Ξ±-Mangostin (Ξ±-M) β’ Bioblast editor: Plangger M β’ O2k-Network Lab: MX Mexico City Pedraza Chaverri J
Labels: MiParea: Respiration, Pharmacology;toxicology
Pathology: Cancer
Organism: Mouse Tissue;cell: Endothelial;epithelial;mesothelial cell Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ET
Pathway: CIV, ROX
HRR: Oxygraph-2k
2023-05