Sirtuin 1-dependent resveratrol cytotoxicity and pro-differentiation activity on breast cancer cells

Deus, Cláudia M.; Serafim, Teresa L.; Magalhães-Novais, Sílvia; Vilaça, Andreia; Moreira, Ana C.; Sardão, Vilma A.; Cardoso, Susana M.; Oliveira, Paulo J.

doi:10.1007/s00204-016-1784-x

Cited by 41 publications

(33 citation statements)

References 57 publications

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“…Currently, several studies have documented that Rev possesses various biological properties, including antioxidant, anti-inflammatory, and anti-proliferative properties, and promotes cell differentiation and apoptosis [27-30]. The data from a recent study showed that Rev reversed the remodelling of the pulmonary vasculature by restoring atrophic gene expression in MCT-induced PH [18].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Protects Against Pulmonary Arterial Hypertension in Rats via Activation of Silent Information Regulator 1

Jia

et al. 2017

Cell Physiol Biochem

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Background/Objectives: The polyphenol resveratrol (Rev) has been found to exhibit various beneficial effects including prevention of pulmonary arterial hypertension (PAH). The present study was designed to investigate the action and potential mechanism of Rev on PAH, focusing on the role of SIRT1 (Silent Information Regulator 1) in apoptosis of pulmonary artery smooth muscle cells (PASMCs). Methods: PAH rats were established by exposure to hypoxia for 21 days. Rev and SRT1720 (a selective SIRT1 activator) were used to reverse PAH by gavaging rats. PASMCs were confronted with hypoxia for 24 h or 48 h and were then treated with Rev or SRT1720 in vitro. Western blot was performed to detect the protein expression of SIRT1. CCK-8 and scratch wound experiments were carried out to verify cell proliferation. In addition, the TUNEL positive assay and flow cytometry assay were used to measure PASMC apoptosis. Mitochondrial permeability transition (mPT) was identified by confocal microscopy. Right ventricular systolic pressure (RVSP) was determined with a Gould pressure transducer, and right ventricular hypertrophy (RVH) was determined by weighing the cardiac muscle. Results: We demonstrated that Rev could reverse the remodelling of the pulmonary vasculature, thus contributing to alleviating the severity of PAH. Down-regulation of SIRT1 was observed in PAH, but administration of Rev had no obvious effect on the protein expression of SIRT1. In addition, Rev could induce mitochondrial swelling and nuclear pyknosis, leading to small, dense, and dysmorphic mitochondria in rats exposed to hypoxia alone. Rev treatment inhibited PASMC proliferation in a dose-dependent manner in vitro. Incubation with SRT1720, a specific activator of SIRT1, significantly retarded PASMC proliferation and promoted PASMC apoptosis in vitro. The mechanism could be associated with inducing mPT damage in PASMCs. Rev and SRT1720 treatment mitigated RVSP and reduced RVH. Conclusion: Rev produced a beneficial effect partially by enhancing the activation of SIRT1, thus improving RVSP and reducing RVH. SIRT1 activation increased PASMC apoptosis by inducing mPT dysfunction, which might be a novel future strategy for the treatment of PAH.

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Section: Discussionmentioning

confidence: 99%

Resveratrol Protects Against Pulmonary Arterial Hypertension in Rats via Activation of Silent Information Regulator 1

Jia

et al. 2017

Cell Physiol Biochem

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“…The Seahorse XF96 Extracellular Flux Analyzer was used for assessment of both cellular oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) as described (Deus et al, 2017). Cells were seeded in XF96 cell culture microplates at 8x10 4 per well in standard culture media.…”

Section: Evaluation Of Respiration and Glycolysismentioning

confidence: 99%

Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Restores Tumor Growth of Respiration-Deficient Cancer Cells

et al. 2019

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“…A well-known dietary antioxidant supplement is resveratrol. Resveratrol is a stilbenoid phenolic compound, with its antioxidant capacity giving it several possible therapeutic applications (Cho et al, 2017b;Ko et al, 2017) Sawda et al, 2017;Truong et al, 2017), including age-related diseases (Lange , Li, 2017;Navarro-Cruz et al, 2017), and cancer (Deus et al, 2017). In fact, resveratrol appears to improve mitochondrial function and biogenesis in skeletal muscle of aged animals (Muhammad , Allam, 2017).…”

Section: Ros Mitochondrial Dna and Agingmentioning

confidence: 99%

Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases

Giorgi

Marchi

Simões

et al. 2018

International Review of Cell and Molecular Biology

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275

162

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Aging has been linked to several degenerative processes that, through the accumulation of molecular and cellular damage, can progressively lead to cell dysfunction and organ failure. Human aging is linked with a higher risk for individuals to develop cancer, neurodegenerative, cardiovascular, and metabolic disorders. The understanding of the molecular basis of aging and associated diseases has been one major challenge of scientific research over the last decades. Mitochondria, the center of oxidative metabolism and principal site of reactive oxygen species (ROS) production, are crucial both in health and in pathogenesis of many diseases. Redox signaling is important for the modulation of cell functions and several studies indicate a dual role for ROS in cell physiology. In fact, high concentrations of ROS are pathogenic and can cause severe damage to cell and organelle membranes, DNA, and proteins. On the other hand, moderate amounts of ROS are essential for the maintenance of several biological processes, including gene expression. In this review, we provide an update regarding the key roles of ROS-mitochondria cross talk in different fundamental physiological or pathological situations accompanying aging and highlighting that mitochondrial ROS may be a decisive target in clinical practice.

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Sirtuin 1-dependent resveratrol cytotoxicity and pro-differentiation activity on breast cancer cells

Cited by 41 publications

References 57 publications

Resveratrol Protects Against Pulmonary Arterial Hypertension in Rats via Activation of Silent Information Regulator 1

Resveratrol Protects Against Pulmonary Arterial Hypertension in Rats via Activation of Silent Information Regulator 1

Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Restores Tumor Growth of Respiration-Deficient Cancer Cells

Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases

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