Sirt3 Exerts Its Tumor-Suppressive Role by Increasing p53 and Attenuating Response to Estrogen in MCF-7 Cells

Pinterić, Marija; Podgorski, Iva I.; Hadžija, Mirko; Filić, Vedrana; Paradžik, Mladen; Proust, Bastien Lucien Jean; Dekanić, Ana; Ciganek, Ivan; Pleše, Denis; Marčinko, Dora; Balog, Tihomir; Sobočanec, Sandra

doi:10.3390/antiox9040294

Cited by 7 publications

(8 citation statements)

References 63 publications

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“…Statistical analysis of data was performed using SPSS (17.0, IBM, Armonk, NY, USA) for Windows as described previously [17]. Significance is set at p<0.05.…”

Section: Resultsmentioning

confidence: 99%

“…For superoxide dismutase (SOD) activity analysis, the RANSOD kit (RANDOX Labs, Crumlin, UK) was used according to the manufacturer's protocol, as described previously [17].…”

Section: Sod Activity Analysismentioning

confidence: 99%

“…Immunocytochemistry staining was performed as described previously [16,17]. MitoTracker Deep Red (100 nM; Thermo Fisher Scientific, Waltham, MA, USA) was added after hyperoxic treatment and cells were incubated for 20 min at 37°C.…”

Section: Immunocytochemistry Fluorescence and Confocal Microscopy Anamentioning

confidence: 99%

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Combination of sirtuin 3 and hyperoxia diminishes tumorigenic properties of MDA-MB-231 cells

et al. 2020

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Aims: Since the role of the major mitochondrial NAD + -dependent deacetylase, sirtuin 3 (Sirt3), is differential in cancer, opposite to the well-known tumor-suppressing effect of hyperoxia, this study aimed to investigate the role of Sirt3 in triple-negative breast cancer (TNBC) cell line MDA-MB-231 upon hyperoxic (95% O2) conditions.Main methods: MDA-MB-231 cells were stably transfected with Flag-tagged Sirt-3 or empty plasmid. Western blot and real-time PCR were used to monitor the expression of proteins or genes involved in mitochondrial biogenesis, metabolic regulation and antioxidant defense. Immunocytochemistry and confocal microscopy were used to confirm the cellular localization and abundance of proteins. Flow cytometry was used to analyze mitochondrial mass, potential and ROS production, and MTT test as a measure of metabolic activity. Mitotic index analysis, colony-forming unit assay, DNA damage and Annexin V-FITC analyses were used to assess the differences in the growth and apoptosis rate.Key findings: Although Sirt3 seemed to improve mitochondrial properties by increasing mitochondrial mass and potential, metabolic activity (Warburg effect) and antioxidative defense (SOD2, Cat), it also increased mitochondrial ROS, induced DNA damage, timp-1 expression, formation of multinucleated cells and apoptosis, and finally markedly reduced the proliferation of MDA-MB-231 cells. All these effects were even more evident upon the hyperoxic treatment, thus pointing towards combined negative effect of Sirt3 and hyperoxia on MDA-MB-231 cells.Significance: Both Sirt3 and hyperoxia, alone or in combination, have the potential to negatively affect the malignant properties of the MDA-MB-231 cells and should be further explored as a possible therapy for TNBC.

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“…Statistical analysis of data was performed using SPSS (17.0, IBM, Armonk, NY, USA) for Windows as described previously [17]. Significance is set at p<0.05.…”

Section: Resultsmentioning

confidence: 99%

“…For superoxide dismutase (SOD) activity analysis, the RANSOD kit (RANDOX Labs, Crumlin, UK) was used according to the manufacturer's protocol, as described previously [17].…”

Section: Sod Activity Analysismentioning

confidence: 99%

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Combination of sirtuin 3 and hyperoxia diminishes tumorigenic properties of MDA-MB-231 cells

et al. 2020

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“…Further supporting the tumor suppressor role of SIRT3 in breast cancer, SIRT3 suppresses estrogen-induced cytosolic and mitochondrial ROS production, diminishes estrogen-induced DNA synthesis, and upregulates p53 expression in MCF-7 breast cancer cells [ 70 ], despite its increasing antioxidant activities and cytosolic ROS. From the above-mentioned studies, it is evident that there is a well-established tumor suppressor role of SIRT3 in breast cancer.…”

Section: Mechanistic Roles Of Sirtuins In Breast and Prostate Cancermentioning

confidence: 98%

The Mechanistic Roles of Sirtuins in Breast and Prostate Cancer

Onyiba¹,

Scarlett

Weidenhofer

2022

Cancers

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Mammalian sirtuins (SIRT1–7) are involved in a myriad of cellular processes, including apoptosis, proliferation, differentiation, epithelial-mesenchymal transition, aging, DNA repair, senescence, viability, survival, and stress response. In this review, we discuss the current information on the mechanistic roles of SIRT1–7 and their downstream effects (tumor promotion or suppression) in cancers of the breast and prostate. Specifically, we highlight the involvement of sirtuins in the regulation of various proteins implicated in proliferation, apoptosis, autophagy, chemoresistance, invasion, migration, and metastasis of breast and prostate cancer. Additionally, we highlight the available information regarding SIRT1–7 regulation by miRNAs, laying much emphasis on the consequences in the progression of breast and prostate cancer.

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“…In this experimental setting, E2 increased levels of glutathione peroxide, SOD1 and SOD2 [ 83 ]. Recently, it has been reported that E2 is also able to increase mitochondrial ROS production in MCF-7C cells [ 84 ].…”

Section: The Interplay Among E2 E2:erα Signaling and Genome Stabmentioning

confidence: 99%

A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity

Pescatori

Berardinelli

Albanesi

et al. 2021

Cancers

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17β-estradiol (E2) regulates human physiology both in females and in males. At the same time, E2 acts as a genotoxic substance as it could induce DNA damages, causing the initiation of cellular transformation. Indeed, increased E2 plasma levels are a risk factor for the development of several types of cancers including breast cancer. This paradoxical identity of E2 undermines the foundations of the physiological definition of “hormone” as E2 works both as a homeostatic regulator of body functions and as a genotoxic compound. Here, (i) the molecular circuitries underlying this double face of E2 are reviewed, and (ii) a possible framework to reconcile the intrinsic discrepancies of the E2 function is reported. Indeed, E2 is a regulator of the DNA damage response, which this hormone exploits to calibrate its genotoxicity with its physiological effects. Accordingly, the genes required to maintain genome integrity belong to the E2-controlled cellular signaling network and are essential for the appearance of the E2-induced cellular effects. This concept requires an “upgrade” to the vision of E2 as a “genotoxic hormone”, which balances physiological and detrimental pathways to guarantee human body homeostasis. Deregulation of this equilibrium between cellular pathways would determine the E2 pathological effects.

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Sirt3 Exerts Its Tumor-Suppressive Role by Increasing p53 and Attenuating Response to Estrogen in MCF-7 Cells

Cited by 7 publications

References 63 publications

Combination of sirtuin 3 and hyperoxia diminishes tumorigenic properties of MDA-MB-231 cells

Combination of sirtuin 3 and hyperoxia diminishes tumorigenic properties of MDA-MB-231 cells

The Mechanistic Roles of Sirtuins in Breast and Prostate Cancer

A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity

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