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
hybrid, Hybrid Gold
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