Beneficial Oxidative Stress-Related trans-Resveratrol Effects in the Treatment and Prevention of Breast Cancer
Abstract
:1. Introduction
2. Sources and Absorption of Resveratrol
3. Resveratrol and Free Radicals
3.1. Resveratrol and the Nrf2/ARE Pathway
3.2. Resveratrol and PTEN in the PI3K/Akt/mTOR Signaling Pathway
3.3. Effect of Resveratrol on Other Carcinogenic Pathways
3.4. Other Effects
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Ragusa, A.; Centonze, C.; Grasso, M.E.; Latronico, M.F.; Mastrangelo, P.F.; Fanizzi, F.P.; Maffia, M. Composition and Statistical Analysis of Biophenols in Apulian Italian EVOOs. Foods 2017, 6, 90. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gutiérrez-Escobar, R.; Aliaño-González, M.J.; Cantos-Villar, E. Wine Polyphenol Content and Its Influence on Wine Quality and Properties: A Review. Molecules 2021, 26, 718. [Google Scholar] [CrossRef] [PubMed]
- Khan, J.; Deb, P.K.; Priya, S.; Medina, K.D.; Devi, R.; Walode, S.G.; Rudrapal, M. Dietary Flavonoids: Cardioprotective Potential with Antioxidant Effects and Their Pharmacokinetic, Toxicological and Therapeutic Concerns. Molecules 2021, 26, 4021. [Google Scholar] [CrossRef] [PubMed]
- Fraga, C.G.; Croft, K.D.; Kennedy, D.O.; Tomás-Barberán, F.A. The effects of polyphenols and other bioactives on human health. Food Funct. 2019, 10, 514–528. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pradhan, B.; Nayak, R.; Patra, S.; Jit, B.P.; Ragusa, A.; Jena, M. Bioactive Metabolites from Marine Algae as Potent Pharmacophores against Oxidative Stress-Associated Human Diseases: A Comprehensive Review. Molecules 2020, 26, 37. [Google Scholar] [CrossRef]
- Mallamaci, R.; Budriesi, R.; Clodoveo, M.L.; Biotti, G.; Micucci, M.; Ragusa, A.; Curci, F.; Muraglia, M.; Corbo, F.; Franchini, C. Olive Tree in Circular Economy as a Source of Secondary Metabolites Active for Human and Animal Health Beyond Oxidative Stress and Inflammation. Molecules 2021, 26, 1072. [Google Scholar] [CrossRef] [PubMed]
- Pradhan, B.; Patra, S.; Behera, C.; Nayak, R.; Jit, B.P.; Ragusa, A.; Jena, M. Preliminary Investigation of the Antioxidant, Anti-Diabetic, and Anti-Inflammatory Activity of Enteromorpha intestinalis Extracts. Molecules 2021, 26, 1171. [Google Scholar] [CrossRef]
- Takaoka, M.J. Of the phenolic substances of white hellebore (Veratrum grandiflorum Loes. fil.). J. Faculty Sci. Hokkaido Imperial Univ. 1940, 3, 1–16. [Google Scholar]
- Jang, M.; Cai, L.; Udeani, G.O.; Slowing, K.V.; Thomas, C.F.; Beecher, C.W.; Fong, H.H.; Farnsworth, N.R.; Kinghorn, A.D.; Mehta, R.G.; et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997, 275, 218–220. [Google Scholar] [CrossRef] [Green Version]
- Orallo, F. Comparative studies of the antioxidant effects of cis- and trans-resveratrol. Curr. Med. Chem. 2006, 13, 87–98. [Google Scholar] [CrossRef] [PubMed]
- Allen, M.T.; Whitten, D.G. The photophysics and photochemistry of .alpha.,.omega.-diphenylpolyene singlet states. Chem. Rev. 1989, 89, 1691–1702. [Google Scholar] [CrossRef]
- Tosato, M.G.; Vicendo, P.; Thomas, A.H.; Lorente, C. Clearing up the photochemistry of resveratrol: Effect of the solvent. J. Photochem. Photobiol. A Chem. 2018, 367, 327–331. [Google Scholar] [CrossRef] [Green Version]
- Graf, B.A.; Milbury, P.E.; Blumberg, J.B. Flavonols, flavones, flavanones, and human health: Epidemiological evidence. J. Med. Food 2005, 8, 281–290. [Google Scholar] [CrossRef] [PubMed]
- Salehi, B.; Mishra, A.P.; Nigam, M.; Sener, B.; Kilic, M.; Sharifi-Rad, M.; Fokou, P.V.T.; Martins, N.; Sharifi-Rad, J. Resveratrol: A Double-Edged Sword in Health Benefits. Biomedicines 2018, 6, 91. [Google Scholar] [CrossRef] [Green Version]
- Andreani, C.; Bartolacci, C.; Wijnant, K.; Crinelli, R.; Bianchi, M.; Magnani, M.; Hysi, A.; Iezzi, M.; Amici, A.; Marchini, C. Resveratrol fuels HER2 and ERα-positive breast cancer behaving as proteasome inhibitor. Aging 2017, 9, 508–523. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gianchecchi, E.; Fierabracci, A. Insights on the Effects of Resveratrol and Some of Its Derivatives in Cancer and Autoimmunity: A Molecule with a Dual Activity. Antioxidants 2020, 9, 91. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Walle, T.; Hsieh, F.; DeLegge, M.H.; Oatis, J.E., Jr.; Walle, U.K. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab. Dispos. 2004, 32, 1377–1382. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Machado, N.D.; Fernández, M.A.; Díaz, D.D. Recent Strategies in Resveratrol Delivery Systems. ChemPlusChem 2019, 84, 951–973. [Google Scholar] [CrossRef] [PubMed]
- Ferretta, A.; Gaballo, A.; Tanzarella, P.; Piccoli, C.; Capitanio, N.; Nico, B.; Annese, T.; Di Paola, M.; Dell’aquila, C.; De Mari, M.; et al. Effect of resveratrol on mitochondrial function: Implications in parkin-associated familiar Parkinson’s disease. Biochim. Biophys. Acta 2014, 1842, 902–915. [Google Scholar] [CrossRef] [Green Version]
- Vergara, D.; Gaballo, A.; Signorile, A.; Ferretta, A.; Tanzarella, P.; Pacelli, C.; Di Paola, M.; Cocco, T.; Maffia, M. Resveratrol Modulation of Protein Expression in parkin-Mutant Human Skin Fibroblasts: A Proteomic Approach. Oxid. Med. Cell. Longev. 2017, 2017, 2198243. [Google Scholar] [CrossRef] [Green Version]
- Valko, M.; Izakovic, M.; Mazur, M.; Rhodes, C.J.; Telser, J. Role of oxygen radicals in DNA damage and cancer incidence. Mol. Cell. Biochem. 2004, 266, 37–56. [Google Scholar] [CrossRef] [PubMed]
- Valavanidis, A.; Vlachogianni, T.; Fiotakis, C. 8-hydroxy-2’-deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev. 2009, 27, 120–139. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hayes, J.D.; Dinkova-Kostova, A.T.; Tew, K.D. Oxidative Stress in Cancer. Cancer Cell. 2020, 38, 167–197. [Google Scholar] [CrossRef]
- Essick, E.E.; Sam, F. Oxidative stress and autophagy in cardiac disease, neurological disorders, aging and cancer. Oxid. Med. Cell. Longev. 2010, 3, 168–177. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kiyokawa, H.; Hoshino, Y.; Sakaguchi, K.; Muro, S.; Yodoi, J. Redox Regulation in Aging Lungs and Therapeutic Implications of Antioxidants in COPD. Antioxidants 2021, 10, 1429. [Google Scholar] [CrossRef] [PubMed]
- Gloire, G.; Legrand-Poels, S.; Piette, J. NF-kappaB activation by reactive oxygen species: Fifteen years later. Biochem. Pharmacol. 2006, 72, 1493–1505. [Google Scholar] [CrossRef] [PubMed]
- Simon, A.R.; Rai, U.; Fanburg, B.L.; Cochran, B.H. Activation of the JAK-STAT pathway by reactive oxygen species. Am. J. Physiol. 1998, 275, 1640–1652. [Google Scholar] [CrossRef] [PubMed]
- Görlach, A.; Kietzmann, T. Superoxide and derived reactive oxygen species in the regulation of hypoxia-inducible factors. Methods Enzymol. 2007, 435, 421–446. [Google Scholar] [CrossRef]
- Liu, B.; Chen, Y.; St Clair, D.K. ROS and p53: A versatile partnership. Free Radic. Biol. Med. 2008, 44, 1529–1535. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wardyn, J.D.; Ponsford, A.H.; Sanderson, C.M. Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways. Biochem. Soc. Trans. 2015, 43, 621–626. [Google Scholar] [CrossRef] [Green Version]
- Kamiya, T.; Goto, A.; Kurokawa, E.; Hara, H.; Adachi, T. Cross Talk Mechanism among EMT, ROS, and Histone Acetylation in Phorbol Ester-Treated Human Breast Cancer MCF-7 Cells. Oxid. Med. Cell. Longev. 2016, 2016, 1284372. [Google Scholar] [CrossRef] [Green Version]
- Brooks, S.A.; Lomax-Browne, H.J.; Carter, T.M.; Kinch, C.E.; Hall, D.M. Molecular interactions in cancer cell metastasis. Acta Histochem. 2010, 112, 3–25. [Google Scholar] [CrossRef]
- Yang, J. The role of reactive oxygen species in angiogenesis and preventing tissue injury after brain ischemia. Microvasc. Res. 2019, 123, 62–67. [Google Scholar] [CrossRef] [PubMed]
- Dewhirst, M.W.; Cao, Y.; Moeller, B. Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat. Rev. Cancer 2008, 8, 425–437. [Google Scholar] [CrossRef] [Green Version]
- Simon, H.U.; Haj-Yehia, A.; Levi-Schaffer, F. Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 2000, 5, 415–418. [Google Scholar] [CrossRef]
- Aggarwal, V.; Tuli, H.S.; Varol, A.; Thakral, F.; Yerer, M.B.; Sak, K.; Varol, M.; Jain, A.; Khan, M.A.; Sethi, G. Role of Reactive Oxygen Species in Cancer Progression: Molecular Mechanisms and Recent Advancements. Biomolecules 2019, 9, 735. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lima, S.M.; Kehm, R.D.; Terry, M.B. Global breast cancer incidence and mortality trends by region, age-groups, and fertility patterns. EClinicalMedicine 2021, 38, 100985. [Google Scholar] [CrossRef]
- Feng, Y.; Spezia, M.; Huang, S.; Yuan, C.; Zeng, Z.; Zhang, L.; Ji, X.; Liu, W.; Huang, B.; Luo, W.; et al. Breast cancer development and progression: Risk factors, cancer stem cells, signaling, pathways, genomics, and molecular pathogenesis. Genes Dis. 2018, 5, 77–106. [Google Scholar] [CrossRef] [PubMed]
- Yersal, O.; Barutca, S. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J. Clin. Oncol. 2014, 5, 412–424. [Google Scholar] [CrossRef] [PubMed]
- Burguin, A.; Diorio, C.; Durocher, F. Breast Cancer Treatments: Updates and New Challenges. J. Pers. Med. 2021, 11, 808. [Google Scholar] [CrossRef] [PubMed]
- Ragusa, A.; Centonze, C.; Grasso, M.E.; Latronico, M.F.; Mastrangelo, P.F.; Sparascio, F.; Fanizzi, F.P.; Maffia, M. A Comparative Study of Phenols in Apulian Italian Wines. Foods 2017, 6, 24. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ragusa, A.; Centonze, C.; Grasso, M.E.; Latronico, M.F.; Mastrangelo, P.F.; Sparascio, F.; Maffia, M. HPLC Analysis of Phenols in Negroamaro and Primitivo Red Wines from Salento. Foods 2019, 8, 45. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ramírez-Garza, S.L.; Laveriano-Santos, E.P.; Marhuenda-Muñoz, M.; Storniolo, C.E.; Tresserra-Rimbau, A.; Vallverdú-Queralt, A.; Lamuela-Raventós, R.M. Health Effects of Resveratrol: Results from Human Intervention Trials. Nutrients 2018, 10, 1892. [Google Scholar] [CrossRef] [Green Version]
- Briskey, D.; Rao, A. Trans-Resveratrol Oral Bioavailability in Humans Using LipiSperse™ Dispersion Technology. Pharmaceutics 2020, 12, 1190. [Google Scholar] [CrossRef]
- Gambini, J.; Inglés, M.; Olaso, G.; Lopez-Grueso, R.; Bonet-Costa, V.; Gimeno-Mallench, L.; Mas-Bargues, C.; Abdelaziz, K.M.; Gomez-Cabrera, M.C.; Vina, J.; et al. Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans. Oxid. Med. Cell. Longev. 2015, 2015, 837042. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kapetanovic, I.M.; Muzzio, M.; Huang, Z.; Thompson, T.N.; McCormick, D.L. Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats. Cancer Chemother. Pharmacol. 2011, 68, 593–601. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chimento, A.; De Amicis, F.; Sirianni, R.; Sinicropi, M.S.; Puoci, F.; Casaburi, I.; Saturnino, C.; Pezzi, V. Progress to Improve Oral Bioavailability and Beneficial Effects of Resveratrol. Int. J. Mol. Sci. 2019, 20, 1381. [Google Scholar] [CrossRef] [Green Version]
- Zafar, M.S.; Quarta, A.; Marradi, M.; Ragusa, A. Recent Developments in the Reduction of Oxidative Stress through Antioxidant Polymeric Formulations. Pharmaceutics 2019, 11, 505. [Google Scholar] [CrossRef] [Green Version]
- Devi, P.; Sharma, P.; Rathore, C.; Negi, P. Novel Drug Delivery Systems of Resveratrol to Bioavailability and Therapeutic Effects. In Resveratrol—Adding Life to Years, Not Adding Years to Life; Badria, F.A., Ed.; IntechOpen: London, UK, 2019. [Google Scholar] [CrossRef] [Green Version]
- Oliviero, F.; Zamudio-Cuevas, Y.; Belluzzi, E.; Andretto, L.; Scanu, A.; Favero, M.; Ramonda, R.; Ravagnan, G.; López-Reyes, A.; Spinella, P.; et al. Polydatin and Resveratrol Inhibit the Inflammatory Process Induced by Urate and Pyrophosphate Crystals in THP-1 Cells. Foods 2019, 8, 560. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- De Maria, S.; Scognamiglio, I.; Lombardi, A.; Amodio, N.; Caraglia, M.; Cartenì, M.; Ravagnan, G.; Stiuso, P. Polydatin, a natural precursor of resveratrol, induces cell cycle arrest and differentiation of human colorectal Caco-2 cell. J. Transl. Med. 2013, 11, 264. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mikstacka, R.; Rimando, A.M.; Ignatowicz, E. Antioxidant effect of trans-resveratrol, pterostilbene, quercetin and their combinations in human erythrocytes in vitro. Plant. Foods Hum. Nutr. 2010, 65, 57–63. [Google Scholar] [CrossRef] [PubMed]
- Du, Q.; Hu, B.; An, H.M.; Shen, K.P.; Xu, L.; Deng, S.; Wei, M.M. Synergistic anticancer effects of curcumin and resveratrol in Hepa1–6 hepatocellular carcinoma cells. Oncol. Rep. 2013, 29, 1851–1858. [Google Scholar] [CrossRef] [Green Version]
- Fantacuzzi, M.; Gallorini, M.; Gambacorta, N.; Ammazzalorso, A.; Aturki, Z.; Balaha, M.; Carradori, S.; Giampietro, L.; Maccallini, C.; Cataldi, A.; et al. Design, Synthesis and Biological Evaluation of Aromatase Inhibitors Based on Sulfonates and Sulfonamides of Resveratrol. Pharmaceuticals 2021, 14, 984. [Google Scholar] [CrossRef] [PubMed]
- Chow, H.H.; Garland, L.L.; Hsu, C.H.; Vining, D.R.; Chew, W.M.; Miller, J.A.; Perloff, M.; Crowell, J.A.; Alberts, D.S. Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. Cancer Prev. Res. 2010, 3, 1168–1175. [Google Scholar] [CrossRef] [Green Version]
- Leonard, S.S.; Xia, C.; Jiang, B.H.; Stinefelt, B.; Klandorf, H.; Harris, G.K.; Shi, X. Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem. Biophys. Res. Commun. 2003, 309, 1017–1026. [Google Scholar] [CrossRef] [PubMed]
- Martinez, J.; Moreno, J.J. Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production. Biochem. Pharmacol. 2000, 59, 865–870. [Google Scholar] [CrossRef]
- Tang, X.; Tang, P.; Ma, L.; Liu, L. Screening and Evaluation of Xanthine Oxidase Inhibitors from Gnetum parvifolium in China. Molecules 2019, 24, 2671. [Google Scholar] [CrossRef] [Green Version]
- Ciolino, H.P.; Daschner, P.J.; Yeh, G.C. Resveratrol inhibits transcription of CYP1A1 in vitro by preventing activation of the aryl hydrocarbon receptor. Cancer Res. 1998, 58, 5707–5712. [Google Scholar] [PubMed]
- Ciolino, H.P.; Yeh, G.C. Inhibition of aryl hydrocarbon-induced cytochrome P-450 1A1 enzyme activity and CYP1A1 expression by resveratrol. Mol. Pharmacol. 1999, 56, 760–767. [Google Scholar]
- Guthrie, A.R.; Chow, H.S.; Martinez, J.A. Effects of resveratrol on drug- and carcinogen-metabolizing enzymes, implications for cancer prevention. Pharmacol. Res. Perspect. 2017, 5, e00294. [Google Scholar] [CrossRef]
- Subbaramaiah, K.; Chung, W.J.; Michaluart, P.; Telang, N.; Tanabe, T.; Inoue, H.; Jang, M.; Pezzuto, J.M.; Dannenberg, A.J. Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. J. Biol. Chem. 1998, 273, 21875–21882. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chatterjee, M.; Das, S.; Janarthan, M.; Ramachandran, H.K.; Chatterjee, M. Role of 5-lipoxygenase in resveratrol mediated suppression of 7,12-dimethylbenz(α)anthracene-induced mammary carcinogenesis in rats. Eur. J. Pharmacol. 2011, 668, 99–106. [Google Scholar] [CrossRef]
- Boo, Y.C. Human Skin Lightening Efficacy of Resveratrol and Its Analogs: From in Vitro Studies to Cosmetic Applications. Antioxidants 2019, 8, 332. [Google Scholar] [CrossRef] [Green Version]
- Krajka-Kuźniak, V.; Baer-Dubowska, W. Modulation of Nrf2 and NF-κB Signaling Pathways by Naturally Occurring Compounds in Relation to Cancer Prevention and Therapy. Are Combinations Better Than Single Compounds? Int. J. Mol. Sci. 2021, 22, 8223. [Google Scholar] [CrossRef]
- Lu, F.; Zahid, M.; Wang, C.; Saeed, M.; Cavalieri, E.L.; Rogan, E.G. Resveratrol prevents estrogen-DNA adduct formation and neoplastic transformation in MCF-10F cells. Cancer Prev. Res. 2008, 1, 135–145. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hsieh, T.C.; Lu, X.; Wang, Z.; Wu, J.M. Induction of quinone reductase NQO1 by resveratrol in human K562 cells involves the antioxidant response element ARE and is accompanied by nuclear translocation of transcription factor Nrf2. Med. Chem. 2006, 2, 275–285. [Google Scholar] [CrossRef] [PubMed]
- Zahid, M.; Gaikwad, N.W.; Ali, M.F.; Lu, F.; Saeed, M.; Yang, L.; Rogan, E.G.; Cavalieri, E.L. Prevention of estrogen-DNA adduct formation in MCF-10F cells by resveratrol. Free Radic. Biol. Med. 2008, 45, 136–145. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Inglés, M.; Gambini, J.; Miguel, M.G.; Bonet-Costa, V.; Abdelaziz, K.M.; El Alami, M.; Viña, J.; Borrás, C. PTEN mediates the antioxidant effect of resveratrol at nutritionally relevant concentrations. Biomed. Res. Int. 2014, 2014, 580852. [Google Scholar] [CrossRef] [Green Version]
- Akca, H.; Demiray, A.; Aslan, M.; Acikbas, I.; Tokgun, O. Tumour suppressor PTEN enhanced enzyme activity of GPx, SOD and catalase by suppression of PI3K/AKT pathway in non-small cell lung cancer cell lines. J. Enzyme Inhib. Med. Chem. 2013, 28, 539–544. [Google Scholar] [CrossRef] [PubMed]
- He, X.; Wang, Y.; Zhu, J.; Orloff, M.; Eng, C. Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling. Cancer Lett. 2011, 301, 168–176. [Google Scholar] [CrossRef] [PubMed]
- Ma, R.; Yu, D.; Peng, Y.; Yi, H.; Wang, Y.; Cheng, T.; Shi, B.; Yang, G.; Lai, W.; Wu, X.; et al. Resveratrol induces AMPK and mTOR signaling inhibition-mediated autophagy and apoptosis in multiple myeloma cells. Acta Biochim. Biophys. Sin. 2021, 53, 775–783. [Google Scholar] [CrossRef]
- Das, J.; Ramani, R.; Suraju, M.O. Polyphenol Compounds and PKC Signaling. Biochim. Biophys. Acta 2016, 1860, 2107–2121. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bhardwaj, A.; Sethi, G.; Vadhan-Raj, S.; Bueso-Ramos, C.; Takada, Y.; Gaur, U.; Nair, A.S.; Shishodia, S.; Aggarwal, B.B. Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells. Blood 2007, 109, 2293–2302. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Benitez, D.A.; Hermoso, M.A.; Pozo-Guisado, E.; Fernández-Salguero, P.M.; Castellón, E.A. Regulation of cell survival by resveratrol involves inhibition of NF-kappa B-regulated gene expression in prostate cancer cells. Prostate 2009, 69, 1045–1054. [Google Scholar] [CrossRef] [PubMed]
- Sun, C.; Hu, Y.; Liu, X.; Wu, T.; Wang, Y.; He, W.; Wei, W. Resveratrol downregulates the constitutional activation of nuclear factor-kappaB in multiple myeloma cells, leading to suppression of proliferation and invasion, arrest of cell cycle, and induction of apoptosis. Cancer Genet. Cytogenet. 2006, 165, 9–19. [Google Scholar] [CrossRef]
- Lucas, J.; Hsieh, T.C.; Halicka, H.D.; Darzynkiewicz, Z.; Wu, J.M. Upregulation of PD-L1 expression by resveratrol and piceatannol in breast and colorectal cancer cells occurs via HDAC3/p300-mediated NF-κB signaling. Int. J. Oncol. 2018, 53, 1469–1480. [Google Scholar] [CrossRef] [Green Version]
- Yang, M.; Li, Z.; Tao, J.; Hu, H.; Li, Z.; Zhang, Z.; Cheng, F.; Sun, Y.; Zhang, Y.; Yang, J.; et al. Resveratrol induces PD-L1 expression through snail-driven activation of Wnt pathway in lung cancer cells. J. Cancer Res. Clin. Oncol. 2021, 147, 1101–1113. [Google Scholar] [CrossRef]
- Verdura, S.; Cuyàs, E.; Cortada, E.; Brunet, J.; Lopez-Bonet, E.; Martin-Castillo, B.; Bosch-Barrera, J.; Encinar, J.A.; Menendez, J.A. Resveratrol targets PD-L1 glycosylation and dimerization to enhance antitumor T-cell immunity. Aging 2020, 12, 8–34. [Google Scholar] [CrossRef] [Green Version]
- Sun, Y.; Zhou, Q.M.; Lu, Y.Y.; Zhang, H.; Chen, Q.L.; Zhao, M.; Su, S.B. Resveratrol Inhibits the Migration and Metastasis of MDA-MB-231 Human Breast Cancer by Reversing TGF-β1-Induced Epithelial-Mesenchymal Transition. Molecules 2019, 24, 1131. [Google Scholar] [CrossRef] [Green Version]
- Trapp, V.; Parmakhtiar, B.; Papazian, V.; Willmott, L.; Fruehauf, J.P. Anti-angiogenic effects of resveratrol mediated by decreased VEGF and increased TSP1 expression in melanoma-endothelial cell co-culture. Angiogenesis 2010, 13, 305–315. [Google Scholar] [CrossRef] [Green Version]
- Liang, Z.J.; Wan, Y.; Zhu, D.D.; Wang, M.X.; Jiang, H.M.; Huang, D.L.; Luo, L.F.; Chen, M.J.; Yang, W.P.; Li, H.M.; et al. Resveratrol Mediates the Apoptosis of Triple Negative Breast Cancer Cells by Reducing POLD1 Expression. Front. Oncol. 2021, 11, 569295. [Google Scholar] [CrossRef]
- Huang, C.; Ma, W.Y.; Goranson, A.; Dong, Z. Resveratrol suppresses cell transformation and induces apoptosis through a p53-dependent pathway. Carcinogenesis 1999, 20, 237–242. [Google Scholar] [CrossRef] [Green Version]
- Wu, H.; Chen, L.; Zhu, F.; Han, X.; Sun, L.; Chen, K. The Cytotoxicity Effect of Resveratrol: Cell Cycle Arrest and Induced Apoptosis of Breast Cancer 4T1 Cells. Toxins 2019, 11, 731. [Google Scholar] [CrossRef] [Green Version]
- Arena, A.; Romeo, M.A.; Benedetti, R.; Masuelli, L.; Bei, R.; Gilardini Montani, M.S.; Cirone, M. New Insights into Curcumin- and Resveratrol-Mediated Anti-Cancer Effects. Pharmaceuticals 2021, 14, 1068. [Google Scholar] [CrossRef]
- Chen, Q.; Ganapathy, S.; Singh, K.P.; Shankar, S.; Srivastava, R.K. Resveratrol induces growth arrest and apoptosis through activation of FOXO transcription factors in prostate cancer cells. PLoS ONE 2010, 5, e15288. [Google Scholar] [CrossRef] [PubMed]
- Jin, X.; Wei, Y.; Liu, Y.; Lu, X.; Ding, F.; Wang, J.; Yang, S. Resveratrol promotes sensitization to Doxorubicin by inhibiting epithelial-mesenchymal transition and modulating SIRT1/β-catenin signaling pathway in breast cancer. Cancer Med. 2019, 8, 1246–1257. [Google Scholar] [CrossRef] [Green Version]
- Yang, T.; Zhou, R.; Yu, S.; Yu, S.; Cui, Z.; Hu, P.; Liu, J.; Qiao, Q.; Zhang, J. Cytoplasmic SIRT1 inhibits cell migration and invasion by impeding epithelial-mesenchymal transition in ovarian carcinoma. Mol. Cell. Biochem. 2019, 459, 157–169. [Google Scholar] [CrossRef] [Green Version]
- Chao, S.C.; Chen, Y.J.; Huang, K.H.; Kuo, K.L.; Yang, T.H.; Huang, K.Y.; Wang, C.C.; Tang, C.H.; Yang, R.S.; Liu, S.H. Induction of sirtuin-1 signaling by resveratrol induces human chondrosarcoma cell apoptosis and exhibits antitumor activity. Sci. Rep. 2017, 7, 3180. [Google Scholar] [CrossRef] [PubMed]
- Wu, M.; Ma, L.; Xue, L.; Ye, W.; Lu, Z.; Li, X.; Jin, Y.; Qin, X.; Chen, D.; Tang, W.; et al. Resveratrol alleviates chemotherapy-induced oogonial stem cell apoptosis and ovarian aging in mice. Aging 2019, 11, 1030–1044. [Google Scholar] [CrossRef]
- Brockmueller, A.; Sameri, S.; Liskova, A.; Zhai, K.; Varghese, E.; Samuel, S.M.; Büsselberg, D.; Kubatka, P.; Shakibaei, M. Resveratrol’s Anti-Cancer Effects through the Modulation of Tumor Glucose Metabolism. Cancers 2021, 13, 188. [Google Scholar] [CrossRef]
- Gomez, L.S.; Zancan, P.; Marcondes, M.C.; Ramos-Santos, L.; Meyer-Fernandes, J.R.; Sola-Penna, M.; Da Silva, D. Resveratrol decreases breast cancer cell viability and glucose metabolism by inhibiting 6-phosphofructo-1-kinase. Biochimie 2013, 95, 1336–1343. [Google Scholar] [CrossRef] [Green Version]
- Qasem, R.J. The estrogenic activity of resveratrol: A comprehensive review of in vitro and in vivo evidence and the potential for endocrine disruption. Crit. Rev. Toxicol. 2020, 50, 439–462. [Google Scholar] [CrossRef]
- Cavalieri, E.; Rogan, E. The 3,4-Quinones of Estrone and Estradiol Are the Initiators of Cancer whereas Resveratrol and N-acetylcysteine Are the Preventers. Int. J. Mol. Sci. 2021, 22, 8238. [Google Scholar] [CrossRef] [PubMed]
- van der Zanden, S.Y.; Qiao, X.; Neefjes, J. New insights into the activities and toxicities of the old anticancer drug doxorubicin. FEBS J. 2020, in press. [Google Scholar] [CrossRef] [PubMed]
- Tatlidede, E.; Sehirli, O.; Velioğlu-Oğünc, A.; Cetinel, S.; Yeğen, B.C.; Yarat, A.; Süleymanoğlu, S.; Sener, G. Resveratrol treatment protects against doxorubicin-induced cardiotoxicity by alleviating oxidative damage. Free Radic. Res. 2009, 43, 195–205. [Google Scholar] [CrossRef] [PubMed]
- Gu, J.; Hu, W.; Song, Z.P.; Chen, Y.G.; Zhang, D.D.; Wang, C.Q. Resveratrol-induced autophagy promotes survival and attenuates doxorubicin-induced cardiotoxicity. Int. Immunopharmacol. 2016, 32, 1–7. [Google Scholar] [CrossRef]
- Ruan, Y.; Dong, C.; Patel, J.; Duan, C.; Wang, X.; Wu, X.; Cao, Y.; Pu, L.; Lu, D.; Shen, T.; et al. SIRT1 suppresses doxorubicin-induced cardiotoxicity by regulating the oxidative stress and p38MAPK pathways. Cell. Physiol. Biochem. 2015, 35, 1116–1124. [Google Scholar] [CrossRef]
- Komorowska, D.; Gajewska, A.; Hikisz, P.; Bartosz, G.; Rodacka, A. Comparison of the Effects of Resveratrol and Its Derivatives on the Radiation Response of MCF-7 Breast Cancer Cells. Int. J. Mol. Sci. 2021, 22, 9511. [Google Scholar] [CrossRef] [PubMed]
- Kensler, T.W.; Wakabayashi, N. Nrf2: Friend or foe for chemoprevention? Carcinogenesis 2010, 31, 90–99. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Singh, B.; Bhat, N.K.; Bhat, H.K. Induction of NAD(P)H-quinone oxidoreductase 1 by antioxidants in female ACI rats is associated with decrease in oxidative DNA damage and inhibition of estrogen-induced breast cancer. Carcinogenesis 2012, 33, 156–163. [Google Scholar] [CrossRef] [Green Version]
- Dawling, S.; Roodi, N.; Parl, F.F. Methoxyestrogens exert feedback inhibition on cytochrome P450 1A1 and 1B1. Cancer Res. 2003, 63, 3127–3132. [Google Scholar] [PubMed]
- Cooper, A.J.L.; Hanigan, M.H. Metabolism of Glutathione S-Conjugates: Multiple Pathways. In Comprehensive Toxicology, 3rd ed.; McQueen, C.A., Ed.; Elsevier: Oxford, UK, 2018; pp. 363–406. [Google Scholar]
- Yasuda, M.T.; Sakakibara, H.; Shimoi, K. Estrogen- and stress-induced DNA damage in breast cancer and chemoprevention with dietary flavonoid. Genes Environ. 2017, 39, 10. [Google Scholar] [CrossRef] [Green Version]
- Miricescu, D.; Totan, A.; Stanescu, S., II; Badoiu, S.C.; Stefani, C.; Greabu, M. PI3K/AKT/mTOR Signaling Pathway in Breast Cancer: From Molecular Landscape to Clinical Aspects. Int. J. Mol. Sci. 2020, 22, 173. [Google Scholar] [CrossRef] [PubMed]
- Paplomata, E.; O’Regan, R. The PI3K/AKT/mTOR pathway in breast cancer: Targets, trials and biomarkers. Ther. Adv. Med. Oncol. 2014, 6, 154–166. [Google Scholar] [CrossRef] [Green Version]
- Xie, Y.; Shi, X.; Sheng, K.; Han, G.; Li, W.; Zhao, Q.; Jiang, B.; Feng, J.; Li, J.; Gu, Y. PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia. Mol. Med. Rep. 2019, 19, 783–791. [Google Scholar] [CrossRef] [Green Version]
- Chen, C.-Y.; Chen, J.; He, L.; Stiles, B.L. PTEN: Tumor Suppressor and Metabolic Regulator. Front. Endocrinol. 2018, 9, 338. [Google Scholar] [CrossRef] [Green Version]
- Zou, Z.; Tao, T.; Li, H.; Zhu, X. mTOR signaling pathway and mTOR inhibitors in cancer: Progress and challenges. Cell Biosci. 2020, 10, 31. [Google Scholar] [CrossRef]
- Tong, C.W.S.; Wu, M.; Cho, W.C.S.; To, K.K.W. Recent Advances in the Treatment of Breast Cancer. Front. Oncol. 2018, 8, 227. [Google Scholar] [CrossRef] [Green Version]
- Zuckerman, V.; Wolyniec, K.; Sionov, R.V.; Haupt, S.; Haupt, Y. Tumour suppression by p53: The importance of apoptosis and cellular senescence. J. Pathol. 2009, 219, 3–15. [Google Scholar] [CrossRef] [PubMed]
- Fu, Z.; Tindall, D.J. FOXOs, cancer and regulation of apoptosis. Oncogene 2008, 27, 2312–2319. [Google Scholar] [CrossRef] [Green Version]
- Vander Heiden, M.G.; Cantley, L.C.; Thompson, C.B. Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science 2009, 324, 1029–1033. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Al-jubori, A.A.; Sulaiman, G.M.; Tawfeeq, A.T.; Mohammed, H.A.; Khan, R.A.; Mohammed, S.A.A. Layer-by-Layer Nanoparticles of Tamoxifen and Resveratrol for Dual Drug Delivery System and Potential Triple-Negative Breast Cancer Treatment. Pharmaceutics 2021, 13, 1098. [Google Scholar] [CrossRef]
- Yang, M.D.; Sun, Y.; Zhou, W.J.; Xie, X.Z.; Zhou, Q.M.; Lu, Y.Y.; Su, S.B. Resveratrol Enhances Inhibition Effects of Cisplatin on Cell Migration and Invasion and Tumor Growth in Breast Cancer MDA-MB-231 Cell Models In Vivo and In Vitro. Molecules 2021, 26, 2204. [Google Scholar] [CrossRef]
Direct Effect | Indirect Effect | Physiological Impact | Ref. |
---|---|---|---|
Scavenging of superoxide, hydroxyl, nitric oxide, and peroxynitrate radicals | Reduction of ROS | Elimination of free radicals | [56,57] |
Non-competitive inhibition of XO | Reduction of superoxide radicals | [58] | |
Blocking transcription through the AhR signaling pathway | Inhibition of CYP1A1 gene expression | [59,60] | |
Inhibition of the dimerization of the ligand-AhR complex, its binding to XRE sequences or the recruitment of RNA polymerase II | [61] | ||
Inhibition of the PKC signal transduction pathway | Inhibition of COX-2 gene expression | [62] | |
Increased TGF-β1 expression | Inhibition of 5-LOX | [63] | |
PI3K/Akt mechanism activation | Phosphorylation of Nrf2 | Stimulation of the Nrf2/ARE pathway | [64,65] |
Activation of NQO1 | Reduction of quinones to catechols and subsequent inactivation by the COMT enzyme | [66,67,68] | |
Increased concentration of PTEN | Upregulation of CAT and MnSOD mRNA levels | Decreased concentration of H2O2 | [69,70] |
Suppression of Akt phosphorylation | Inhibition of the mTOR/p70S6K pathway | PI3K survival signaling pathway block | [71,72] |
Inhibition of STAT3 and NF-kB | Inhibition of numerous kinases (e.g., PKC, MAPK, IKK) and some transcription factors (e.g., NF-kB, STAT3, HIF-1α, and AP-1) | Down-regulation of cancer cell proliferation | [73,74] |
Inhibition of IKK | Increased expression of I-kBα, inactivation of NF-kB and its retention in the cytoplasm | [75] | |
Block of the activation of NF-kB induced by IL-1β and TNF-α | Suppression of cell proliferation, apoptosis, angiogenesis, and formation of metastases | [76] | |
HDAC3/p300-mediated NF-kB signaling | Increased expression of PD-L1 | [77] | |
SIRT1 activation | Enhanced binding of β-catenin/TCF to PD-L1 promoter | [78] | |
PD-L1 glycosylation and dimerization | Enhanced anti-tumor T-cell immunity | [79] | |
Inhibition of TGF-β1 activation | Inhibition of the EMT process | [80] | |
Reduced expression of POLD1, VEGF, and HIF-1α | Inhibition of anti-apoptotic proteins and activation of pro-apoptotic ones | Reduced angiogenesis | [81,82] |
Phosphorylation or acetylation of p53 at the level of the serine residue 15 | Increased expression of pro-apoptotic proteins; activation of effector caspases and decreased expression of anti-apoptotic proteins | Induced arrest of the cell cycle at the level of the G0/G1 and S phase | [83,84] |
Phosphorylation of mTOR targets 4EBP1 and P70S6K | Reduction of cancer cells’ basal autophagy used to counteract their basal stress | Increased ROS production | [85] |
Inhibition of PI3K/Akt-mediated phosphorylation | Decreased phosphorylated levels of FoxO | Overexpression of pro-apoptotic proteins and downregulation of the anti-apoptotic ones | [86] |
Increased SIRT1 expression and decreased β-catenin expression | Reduction of the EMT processes | Inhibited proliferation and migration of cancer cells | [87] |
Deacetylation of the p65 subunit of the NF-kB complex | Promotion of cell death | [88,89] | |
Increased FoxO | Increased SOD | Reduced oxidative stress | [90] |
Inhibition of the activity of PFK | Decreased glucose uptake and glycolytic metabolism | Modulation of glucose metabolism | [91,92] |
Interaction with membrane-bound ERs | Modulation of genomic and non-genomic activities | Modulation of steroidal pathways | [93] |
Inhibition of steroidogenesis and estrogen biosynthesis | |||
Reduction of CYP1B1 activity and, thus, the formation of 4-OHE1(E2) | Prevention of the formation of estrogen-DNA adducts | Potential inhibition of cancer initiation | [94] |
AMPK activation | Increased SOD, CAT, and GSH levels; reduced myeloperoxidase levels | Reduced DOX cardiotoxicity | [95] |
SIRT1 activation | Inhibition of p38MAPK and caspases; activation of cytoprotective autophagy | [96,97] | |
Modulation of PI3K/Akt and NF-kB expressions | Inhibition of cell invasion and migration through EMT | Enhanced anti-tumor effect and reduced side effects of cisplatin | [98] |
Significant decrease in the activity of antioxidant enzymes | Increased ROS generation | Increased apoptotic effect of ionizing radiation treatment | [99] |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Quarta, A.; Gaballo, A.; Pradhan, B.; Patra, S.; Jena, M.; Ragusa, A. Beneficial Oxidative Stress-Related trans-Resveratrol Effects in the Treatment and Prevention of Breast Cancer. Appl. Sci. 2021, 11, 11041. https://doi.org/10.3390/app112211041
Quarta A, Gaballo A, Pradhan B, Patra S, Jena M, Ragusa A. Beneficial Oxidative Stress-Related trans-Resveratrol Effects in the Treatment and Prevention of Breast Cancer. Applied Sciences. 2021; 11(22):11041. https://doi.org/10.3390/app112211041
Chicago/Turabian StyleQuarta, Alessandra, Antonio Gaballo, Biswajita Pradhan, Srimanta Patra, Mrutyunjay Jena, and Andrea Ragusa. 2021. "Beneficial Oxidative Stress-Related trans-Resveratrol Effects in the Treatment and Prevention of Breast Cancer" Applied Sciences 11, no. 22: 11041. https://doi.org/10.3390/app112211041
APA StyleQuarta, A., Gaballo, A., Pradhan, B., Patra, S., Jena, M., & Ragusa, A. (2021). Beneficial Oxidative Stress-Related trans-Resveratrol Effects in the Treatment and Prevention of Breast Cancer. Applied Sciences, 11(22), 11041. https://doi.org/10.3390/app112211041