alpha-Mangostin induces oxidative damage, mitochondrial dysfunction, and apoptosis in a triple-negative breast cancer model


Por: Cruz-Gregorio, Alfredo, Aranda-Rivera, Ana Karina, Aparicio-Trejo, Omar Emiliano, Medina-Campos, Omar Noel, Sciutto, Edda, Fragoso, Gladis, Pedraza-Chaverri, Jose

Publicada: 1 ene 2023 Ahead of Print: 1 abr 2023
Categoría: Pharmacology

Resumen:
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 a-Mangostin (a-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 a-M on redox state, mitochondrial metabolism, and apoptosis in 4T1 mammary carcinoma cells. We found that a-M decreases both protein levels and enzymatic activity of catalase, and increases reactive oxygen species, oxidized proteins and glutathione disulfide, which demonstrates that a-M induces oxidative damage. We also found that a-M promotes mitochondrial dysfunction by abating basal respiration, the respiration ligated to oxidative phosphorylation (OXPHOS), and the rate control of whole 4T1 cells. Additionally, a-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 1a, showing a mitochondrial mass reduction. Then, oxidative damage and mitochondrial dysfunction induced by a-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 a-M induces OS and mitochondrial dysfunction, resulting in 4T1 cell death through apoptotic mechanisms.

Filiaciones:
Cruz-Gregorio, Alfredo:
 Inst Nacl Cardiol Ignacio Chavez, Dept Biomed Cardiovasc, Cdmx 14080, Mexico

 Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Lab F 315, Cdmx 04510, Mexico

 Inst Nacl CardiologiaIgnac Chavez, Dept Biomed Cardiovasc, Juan Badiano 1,Belisario Dominguez Secc 16, Cdmx 14080, Mexico

Aranda-Rivera, Ana Karina:
 Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Lab F 315, Cdmx 04510, Mexico

Aparicio-Trejo, Omar Emiliano:
 Inst Nacl Cardiol Ignacio Chavez, Dept Fisiopatol Cardiorenal, Cdmx 14080, Mexico

Medina-Campos, Omar Noel:
 Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Lab F 315, Cdmx 04510, Mexico

Sciutto, Edda:
 Univ Nacl Autonoma Mexico, Dept Inmunol, Inst Invest Biomed, Cdmx 04510, Mexico

Fragoso, Gladis:
 Univ Nacl Autonoma Mexico, Dept Inmunol, Inst Invest Biomed, Cdmx 04510, Mexico

Pedraza-Chaverri, Jose:
 Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Lab F 315, Cdmx 04510, Mexico
ISSN: 0951418X
Editorial
John Wiley and Sons Ltd, THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND, Estados Unidos America
Tipo de documento: Article
Volumen: 37 Número: 8
Páginas: 3394-3407
WOS Id: 000963822400001
ID de PubMed: 37012651
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