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Antioxidants
Volume 9
Issue 4
10.3390/antiox9040294
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Article

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

by
Marija Pinterić
1,†,
Iva I. Podgorski
1,†,
Marijana Popović Hadžija
1,
Vedrana Filić
2,
Mladen Paradžik
2,3,
Bastien Lucien Jean Proust
1,
Ana Dekanić
1,
Ivan Ciganek
1,
Denis Pleše
1,
Dora Marčinko
1,
Tihomir Balog
1 and
Sandra Sobočanec
1,*
1
Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia
2
Division of Molecular Biology, Ruđer Bošković Institute, 10000 Zagreb, Croatia
3
Department Molecular Biotechnology and Health Sciences, Molecular Biotechnology Centre (MBC), University of Torino, 10124 Torino, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Antioxidants 2020, 9(4), 294; https://doi.org/10.3390/antiox9040294
Submission received: 25 February 2020 / Revised: 21 March 2020 / Accepted: 30 March 2020 / Published: 1 April 2020
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Abstract

Estrogen (E2) is a major risk factor for the initiation and progression of malignancy in estrogen receptor (ER) positive breast cancers, whereas sirtuin 3 (Sirt3), a major mitochondrial NAD+-dependent deacetylase, has the inhibitory effect on the tumorigenic properties of ER positive MCF-7 breast cancer cells. Since it is unclear if this effect is mediated through the estrogen receptor alpha (ERα) signaling pathway, in this study, we aimed to determine if the tumor-suppressive function of Sirt3 in MCF-7 cells interferes with their response to E2. Although we found that Sirt3 improves the antioxidative response and mitochondrial fitness of the MCF-7 cells, it also increases DNA damage along with p53, AIF, and ERα expression. Moreover, Sirt3 desensitizes cells to the proliferative effect of E2, affects p53 by disruption of the ERα–p53 interaction, and decreases proliferation, colony formation, and migration of the cells. Our observations indicate that these tumor-suppressive effects of Sirt3 could be reversed by E2 treatment only to a limited extent which is not sufficient to recover the tumorigenic properties of the MCF-7 cells. This study provides new and interesting insights with respect to the functional role of Sirt3 in the E2-dependent breast cancers.
Keywords: sirtuin 3; MCF-7; estrogen receptor; p53; breast cancer cells sirtuin 3; MCF-7; estrogen receptor; p53; breast cancer cells

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MDPI and ACS Style

Pinterić, M.; Podgorski, I.I.; Hadžija, M.P.; Filić, V.; Paradžik, M.; Proust, B.L.J.; Dekanić, A.; Ciganek, I.; Pleše, D.; Marčinko, D.; et al. Sirt3 Exerts Its Tumor-Suppressive Role by Increasing p53 and Attenuating Response to Estrogen in MCF-7 Cells. Antioxidants 2020, 9, 294. https://doi.org/10.3390/antiox9040294

AMA Style

Pinterić M, Podgorski II, Hadžija MP, Filić V, Paradžik M, Proust BLJ, Dekanić A, Ciganek I, Pleše D, Marčinko D, et al. Sirt3 Exerts Its Tumor-Suppressive Role by Increasing p53 and Attenuating Response to Estrogen in MCF-7 Cells. Antioxidants. 2020; 9(4):294. https://doi.org/10.3390/antiox9040294

Chicago/Turabian Style

Pinterić, Marija, Iva I. Podgorski, Marijana Popović Hadžija, Vedrana Filić, Mladen Paradžik, Bastien Lucien Jean Proust, Ana Dekanić, Ivan Ciganek, Denis Pleše, Dora Marčinko, and et al. 2020. "Sirt3 Exerts Its Tumor-Suppressive Role by Increasing p53 and Attenuating Response to Estrogen in MCF-7 Cells" Antioxidants 9, no. 4: 294. https://doi.org/10.3390/antiox9040294

APA Style

Pinterić, M., Podgorski, I. I., Hadžija, M. P., Filić, V., Paradžik, M., Proust, B. L. J., Dekanić, A., Ciganek, I., Pleše, D., Marčinko, D., Balog, T., & Sobočanec, S. (2020). Sirt3 Exerts Its Tumor-Suppressive Role by Increasing p53 and Attenuating Response to Estrogen in MCF-7 Cells. Antioxidants, 9(4), 294. https://doi.org/10.3390/antiox9040294

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