Resveratrol inhibits cancer cell proliferation by impairing oxidative phosphorylation and inducing oxidative stress

Rodrı́guez-Enrı́quez, Sara; Pacheco-Velázquez, Silvia Cecilia; Marín‐Hernández, Álvaro; Gallardo‐Pérez, Juan Carlos; Robledo‐Cadena, Diana Xochiquetzal; Hernández‐Reséndiz, Ileana; García‐García, Jorge Donato; Belmont-Díaz, Javier A.; López‐Marure, Rebeca; Hernández‐Esquivel, Luz; Sánchez‐Thomas, Rosina; Moreno‐Sánchez, Rafael

doi:10.1016/j.taap.2019.03.008

Cited by 74 publications

(56 citation statements)

References 71 publications

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“…Propagation and isolation of AS-30D ascites hepatoma cells and culture of human cervix cancer HeLa and SiHa cells, human breast cancer MDA-MB-231 and MCF-7 cells, human prostate cancer PC3 and DU145, human lung A549, human colorectal HCT116 and Colo 205 cells, human HFF-1 fibroblasts, and mouse 3T3 fibroblasts were carried out in Dulbecco modified eagle medium (DMEM) plus 25 mM glucose as previously described (51,55,59,(85)(86)(87). All cancer and non-cancer cell lines used were purchased from ATCC and cultured in DMEM (Sigma-Aldrich) supplemented with 10% fetal bovine serum (Biowest, Nuaillé, France) and 10,000 U penicillin/streptomycin (Sigma-Aldrich) and placed under a humidified atmosphere of 5% CO 2 /95% air at 37 • C. Genotyping (INMEGEN, Tlalpan, Mexico city, Mexico) of the cancer cell lines showed >90% of the canonic allelic markers displayed in the ATCC original clones.…”

Section: Cell Growth and Culturementioning

confidence: 99%

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Physiological Role of Glutamate Dehydrogenase in Cancer Cells

et al. 2020

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NH + 4 increased growth rates and final densities of several human metastatic cancer cells. To assess whether glutamate dehydrogenase (GDH) in cancer cells may catalyze the reverse reaction of NH + 4 fixation, its covalent regulation and kinetic parameters were determined under near-physiological conditions. Increased total protein and phosphorylation were attained in NH + 4-supplemented metastatic cells, but total cell GDH activity was unchanged. Higher V max values for the GDH reverse reaction vs. forward reaction in both isolated hepatoma (HepM) and liver mitochondria [rat liver mitochondria (RLM)] favored an NH + 4-fixing role. GDH sigmoidal kinetics with NH + 4 , ADP, and leucine fitted to Hill equation showed n H values of 2 to 3. However, the K 0.5 values for NH + 4 were over 20 mM, questioning the physiological relevance of the GDH reverse reaction, because intracellular NH + 4 in tumors is 1 to 5 mM. In contrast, data fitting to the Monod-Wyman-Changeux (MWC) model revealed lower K m values for NH + 4 , of 6 to 12 mM. In silico analysis made with MWC equation, and using physiological concentrations of substrates and modulators, predicted GDH N-fixing activity in cancer cells. Therefore, together with its thermodynamic feasibility, GDH may reach rates for its reverse, NH + 4-fixing reaction that are compatible with an anabolic role for supporting growth of cancer cells.

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Section: Cell Growth and Culturementioning

confidence: 99%

“…Fresh culture medium with 25 mM glucose ± NH 4 Cl was replaced every 3 days, which helped to discard incompletely formed spheroids. The spheroid growth was determined at the indicated times by measuring MCTS diameter with a calibrated reticule (1/10 mm) in an inverted phase contrast microscope (Zeiss, Thornwood, NY, USA) (86).…”

Section: Cell Growth and Culturementioning

confidence: 99%

Physiological Role of Glutamate Dehydrogenase in Cancer Cells

et al. 2020

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“…Then, cyt C releases into the cytosol to form Apaf1-procaspase-9 complex resulting in apoptotic cell death [144]. In fact, resveratrol stimulates apoptotic cell death through improving the oxidative phosphorylation [145]. The studies approve that the high concentration of resveratrol or long-term exposure to resveratrol is related to a perturbation in the oxidative-antioxidative balance leading to apoptotic cell death [146][147][148][149][150].…”

Section: Resveratrol and Oxidative Stressmentioning

confidence: 99%

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

et al. 2020

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Mitochondria are intracellular organelles with two distinct membranes, known as an outer mitochondrial membrane and inner cell membrane. Originally, mitochondria have been derived from bacteria. The main function of mitochondria is the production of ATP. However, this important organelle indirectly protects cells by consuming oxygen in the route of energy generation. It has been found that mitochondria are actively involved in the induction of the intrinsic pathways of apoptosis. So, there have been efforts to sustain mitochondrial homeostasis and inhibit its dysfunction. Notably, due to the potential role of mitochondria in the stimulation of apoptosis, this organelle is a promising target in cancer therapy. Resveratrol is a non-flavonoid polyphenol that exhibits significant pharmacological effects such as antioxidant, anti-diabetic, anti-inflammatory and anti-tumor. The anti-tumor activity of resveratrol may be a consequence of its effect on mitochondria. Multiple studies have investigated the relationship between resveratrol and mitochondria, and it has been demonstrated that resveratrol is able to significantly enhance the concentration of reactive oxygen species, leading to the mitochondrial dysfunction and consequently, apoptosis induction. A number of signaling pathways such as sirtuin and NF-κB may contribute to the mitochondrial-mediated apoptosis by resveratrol. Besides, resveratrol shifts cellular metabolism from glycolysis into mitochondrial respiration to induce cellular death in cancer cells. In the present review, we discuss the possible interactions between resveratrol and mitochondria, and its potential application in cancer therapy.

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“…Recent studies have shown that the expression of a number of proteins involved in the mitophagy processes, including MFN1, Parkin, BNIP3, and BNIP3L/NIX, is dysregulated in different cancer types [35]. However, the role of mitophagy in tumor development and progression remains largely unclear.…”

Section: Cancermentioning

confidence: 99%

“…The anticancer effects of resveratrol (0.001-1000 μM, for 48 h) on HeLa cells were investigated by Rodríguez-Enríquez et al [35]. In their study, biochemical mechanisms underlying resveratrol-induced inhibition of HeLa cell growth and promotion of HeLa cell death were an excessive cellular ROS production corresponding with a significant decrement in the superoxide dismutase (SOD) activity and glutathione (GSH) levels, a decreased oxidative phosphorylation, and a strong mitophagy activation [35].…”

Section: Cancermentioning

confidence: 99%

Effects of Plant and Animal Natural Products on Mitophagy

Shakeri

Bianconi

Pirro

et al. 2020

Oxidative Medicine and Cellular Longevity

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Mitophagy is a protected cellular process that is essential for autophagic removal of damaged mitochondria and for preservation of a healthy mitochondrial population. In the last years, a particular interest has been devoted in studying the effects of natural compounds on mitophagy. Different natural compounds may modulate mitochondrial oxidative phosphorylation, the production of mitochondrial reactive oxygen species, the expression of mitophagy-and autophagy-related genes, and the activities of transcription factors which regulate the expression of mitochondrial proteins, thereby controlling mitochondrial damage and mitophagy. Remarkably, since mitochondrial function has a crucial role in the pathogenesis of various diseases (e.g., cancer, atherosclerosis, Duchenne muscular dystrophy, diabetes complications, Alzheimer's disease, and hepatic steatosis), these effects might have important therapeutic implications. In this review, preclinical studies investigating the role of different natural compounds in the modulation of mitophagy will be discussed.

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Resveratrol inhibits cancer cell proliferation by impairing oxidative phosphorylation and inducing oxidative stress

Cited by 74 publications

References 71 publications

Physiological Role of Glutamate Dehydrogenase in Cancer Cells

Physiological Role of Glutamate Dehydrogenase in Cancer Cells

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

Effects of Plant and Animal Natural Products on Mitophagy

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