Resveratrol, Rapamycin and Metformin as Modulators of Antiviral Pathways
Abstract
:1. Resveratrol
2. Rapamycin
3. Metformin
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Burns, J.; Yokota, T.; Ashihara, H.; Lean, M.E.J.; Crozier, A. Plant foods and herbal sources of resveratrol. J. Agric. Food Chem. 2002, 50, 3337–3340. [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] [PubMed] [Green Version]
- Walle, T.; Hsieh, F.; DeLegge, M.H.; Oatis, J.E.; 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]
- Walle, T. Bioavailability of resveratrol. Ann. N. Y. Acad. Sci. 2011, 1215, 9–15. [Google Scholar] [CrossRef]
- Pannu, N.; Bhatnagar, A. Resveratrol: From enhanced biosynthesis and bioavailability to multitargeting chronic diseases. Biomed. Pharmacother. 2019, 109, 2237–2251. [Google Scholar] [CrossRef]
- Gambini, J.; Inglés, M.; Lopez-Grueso, R.; Bonet-Costa, V.; Gimeno-Mallench, L.; Mas-Bargues, C. 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] [Green Version]
- Delmas, D.; Aires, V.; Limagne, E.; Dutartre, P.; Mazué, F.; Ghiringhelli, F.; Latruffe, N. Transport, stability, and biological activity of resveratrol. Ann. N. Y. Acad. Sci. 2011, 1215, 48–59. [Google Scholar] [CrossRef]
- Boocock, D.; Patel, K.R.; Faust, G.E.; Normolle, D.P.; Marczylo, T.H.; Crowell, J.A.; Brenner, D.E.; Booth, T.D.; Gescher, A.; Steward, W.P. Quantitation of trans-resveratrol and detection of its metabolites in human plasma and urine by high performance liquid chromatography. J. Chromatogr. B 2007, 848, 182–187. [Google Scholar] [CrossRef] [Green Version]
- Baur, J.A.; Pearson, K.J.; Price, N.L.; Jamieson, H.A.; Lerin, C.; Kalra, A.; Prabhu, V.V.; Allard, J.S.; Lopez-Lluch, G.; Lewis, K.; et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006, 444, 337–342. [Google Scholar] [CrossRef]
- Bhullar, K.S.; Hubbard, B.P. Lifespan and healthspan extension by resveratrol. Biochim. Biophys. Acta 2015, 1852, 1209–1218. [Google Scholar] [CrossRef] [Green Version]
- Pallauf, K.; Rimbach, G.; Rupp, P.M.; Chin, D.; Wolf, I.M.; Rimbacha, G.; Ruppa, P.; China, D. Resveratrol and Lifespan in Model Organisms. Curr. Med. Chem. 2016, 23, 4639–4680. [Google Scholar] [CrossRef]
- Galiniak, S.; Aebisher, D.; Bartusik-Aebisher, D. Health benefits of resveratrol administration. Acta Biochim. Pol. 2019, 66, 13–21. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Breuss, J.M.; Atanasov, A.G.; Uhrin, P. Resveratrol and Its Effects on the Vascular System. Int. J. Mol. Sci. 2019, 20, 1523. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- He, S.; Yan, X. From resveratrol to its derivatives: New sources of natural antioxidant. Curr. Med. Chem. 2013, 20, 1005–1017. [Google Scholar] [PubMed]
- Truong, V.L.; Jun, M.; Jeong, W.S. Role of resveratrol in regulation of cellular defense systems against oxidative stress. Biofactors 2018, 44, 36–49. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.R.; Li, S.; Lin, C.C. Effect of resveratrol and pterostilbene on aging and longevity. Biofactors 2018, 44, 69–82. [Google Scholar] [CrossRef] [PubMed]
- Varoni, E.M.; Lo Faro, A.F.; Sharifi-Rad, J.; Iriti, M. Anticancer Molecular Mechanisms of Resveratrol. Front. Nutr. 2016, 3, 8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dybkowska, E.; Sadowska, A.; Świderski, F.; Rakowska, R.; Wysocka, K. The occurrence of resveratrol in foodstuffs and its potential for supporting cancer prevention and treatment. A review. Rocz. Panstw. Zakl. Hig. 2018, 69, 5–14. [Google Scholar] [PubMed]
- Carter, L.G.; D’Orazio, J.A.; Pearson, K.J. Resveratrol and cancer: Focus on in vivo evidence. Endocr. Relat. Cancer 2014, 21, R209–R225. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jiang, Z.; Chen, K.; Cheng, L.; Yan, B.; Qian, W.; Cao, J.; Liang, C.; Wu, E.; Ma, Q.; Yang, W. Resveratrol and cancer treatment: Updates. Ann. N. Y. Acad. Sci. 2017, 1403, 59–69. [Google Scholar] [CrossRef] [PubMed]
- Ko, J.-H.; Sethi, G.; Um, J.-Y.; Shanmugam, M.K.; Arfuso, F.; Kumar, A.P.; Bishayee, A.; Ahn, K.S. The Role of Resveratrol in Cancer Therapy. Int. J. Mol. Sci. 2017, 18, 2589. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Berman, A.Y.; Motechin, R.A.; Wiesenfeld, M.Y.; Holz, M.K. The therapeutic potential of resveratrol: A review of clinical trials. NPJ Precis. Oncol. 2017, 1, 1–9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Saiko, P.; Akos, S.; Walter, J.; Thomas, S. Resveratrol and its analogs: Defense against cancer, coronary disease and neurodegenerative maladies or just a fad? Mutat. Res. 2008, 658, 68–94. [Google Scholar] [CrossRef] [PubMed]
- de la Lastra, C.A.; Villegas, I. Resveratrol as an anti-inflammatory and anti-aging agent: Mechanisms and clinical implications. Mol. Nutr. Food Res. 2005, 49, 405–430. [Google Scholar] [CrossRef]
- Springer, M.; Moco, M. Resveratrol and Its Human Metabolites-Effects on Metabolic Health and Obesity. Nutrients 2019, 11, 143. [Google Scholar] [CrossRef] [Green Version]
- Pourhanifeh, M.H.; Shafabakhsh, R.; Reiter, R.J.; Asemi, Z. The Effect of Resveratrol on Neurodegenerative Disorders: Possible Protective Actions Against Autophagy, Apoptosis, Inflammation and Oxidative Stress. Curr. Pharm. Des. 2019, 25, 2178–2191. [Google Scholar] [CrossRef]
- Howitz, K.T.; Bitterman, K.J.; Cohen, H.Y.; Lamming, D.W.; Lavu, S.; Wood, J.G.; Zipkin, R.E.; Chung, P.; Kisielewski, A.; Zhang, L.-L.; et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003, 425, 191–196. [Google Scholar] [CrossRef]
- Viswanathan, M.; Kim, S.K.; Berdichevsky, A.; Guarente, L. A Role for SIR-2.1 Regulation of ER Stress Response Genes in Determining C. elegans Life Span. Dev. Cell 2005, 9, 605–615. [Google Scholar] [CrossRef] [Green Version]
- Valenzano, D.R.; Terzibasi, E.; Genade, T.; Cattaneo, A.; Domenici, L. Resveratrol Prolongs Lifespan and Retards the Onset of Age-Related Markers in a Short-Lived Vertebrate. Curr. Biol. 2006, 16, 296–300. [Google Scholar] [CrossRef] [Green Version]
- Abba, Y.; Hassim, H.; Hamzah, H.; Noordin, M.M. Antiviral Activity of Resveratrol against Human and Animal Viruses. Adv. Virol. 2015, 2015, 184241. [Google Scholar] [CrossRef] [Green Version]
- Palamara, A.T.; Nencioni, L.; Aquilano, K.; De Chiara, G.; Hernandez, L.; Cozzolino, F.; Ciriolo, M.R.; Garaci, E. Inhibition of influenza A virus replication by resveratrol. J. Infect. Dis. 2005, 191, 1719–1729. [Google Scholar] [CrossRef] [PubMed]
- Cheng, K.; Wu, Z.; Gao, B.; Xu, J. Analysis of influence of baicalin joint resveratrol retention enema on the TNF-α, SIgA, IL-2, IFN-γ of rats with respiratory syncytial virus infection. Cell Biochem. Biophys. 2014, 70, 1305–1309. [Google Scholar] [CrossRef] [PubMed]
- Liu, T.; Zang, N.; Zhou, N.; Li, W.; Xie, X.; Deng, Y.; Ren, L.; Long, X.; Li, S.; Zhou, L.; et al. Resveratrol inhibits the TRIF-dependent pathway by upregulating sterile alpha and armadillo motif protein, contributing to anti-inflammatory effects after respiratory syncytial virus infection. J. Virol. 2014, 88, 4229–4236. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xie, X.-H.; Zang, N.; Li, S.; Wang, L.-J.; Deng, Y.; He, Y.; Yang, X.-Q.; Liu, E. Resveratrol Inhibits respiratory syncytial virus-induced IL-6 production, decreases viral replication, and downregulates TRIF expression in airway epithelial cells. Inflammation 2012, 35, 1392–1401. [Google Scholar] [CrossRef]
- Zang, N.; Li, S.; Li, W.; Xie, X.; Ren, L.; Long, X.; Xie, J.; Deng, Y.; Fu, Z.; Xu, F.; et al. Resveratrol suppresses persistent airway inflammation and hyperresponsivess might partially via nerve growth factor in respiratory syncytial virus-infected mice. Int. Immunopharmacol. 2015, 28, 121–128. [Google Scholar] [CrossRef]
- Zang, N.; Xie, X.; Deng, Y.; Wu, S.; Wang, L.; Peng, C.; Li, S.; Ni, K.; Luo, Y.; Liu, E. Resveratrol-mediated gamma interferon reduction prevents airway inflammation and airway hyperresponsiveness in respiratory syncytial virus-infected immunocompromised mice. J. Virol. 2011, 85, 13061–13068. [Google Scholar] [CrossRef] [Green Version]
- Filardo, S.; Di Pietro, M.; Mastromarino, P.; Sessa, R. Therapeutic potential of resveratrol against emerging respiratory viral infections. Pharmacol. Ther. 2020, 107613. [Google Scholar] [CrossRef]
- Docherty, J.J.; Sweet, T.J.; Bailey, E.; Faith, S.A.; Booth, T. Resveratrol inhibition of varicella-zoster virus replication in vitro. Antivir. Res. 2006, 72, 171–177. [Google Scholar] [CrossRef]
- Espinoza, J.L.; Takami, A.; Trung, L.Q.; Kato, S.; Nakao, S. Resveratrol prevents EBV transformation and inhibits the outgrowth of EBV-immortalized human B cells. PLoS ONE 2012, 7, e51306. [Google Scholar] [CrossRef] [Green Version]
- Yiu, C.-Y.; Chen, S.-Y.; Chang, L.-K.; Chiu, Y.-F.; Lin, T.-P. Inhibitory effects of resveratrol on the Epstein-Barr virus lytic cycle. Molecules 2010, 15, 7115–7124. [Google Scholar] [CrossRef] [Green Version]
- Chen, X.; Qiao, H.; Liu, T.; Yang, Z.; Xu, L.; Xu, Y.; Ge, H.M.; Tan, R.; Li, E. Inhibition of herpes simplex virus infection by oligomeric stilbenoids through ROS generation. Antivir. Res. 2012, 95, 30–36. [Google Scholar] [CrossRef] [PubMed]
- Docherty, J.; Fu, M.; Hah, J.; Sweet, T.; Faith, S.A.; Booth, T. Effect of resveratrol on herpes simplex virus vaginal infection in the mouse. Antivir. Res. 2005, 67, 155–162. [Google Scholar] [CrossRef] [PubMed]
- Docherty, J.J.; Fu, M.M.H.; Stiffler, B.S.; Limperos, R.J.; Pokabla, C.M.; DeLucia, A.L. Resveratrol inhibition of herpes simplex virus replication. Antivir. Res. 1999, 43, 145–155. [Google Scholar] [CrossRef]
- Docherty, J.J.; Smith, J.S.; Fu, M.M.; Stoner, T.; Booth, T. Effect of topically applied resveratrol on cutaneous herpes simplex virus infections in hairless mice. Antivir. Res. 2004, 61, 19–26. [Google Scholar] [CrossRef]
- Clouser, C.L.; Chauhan, J.; Bess, M.A.; Van Oploo, J.L.; Zhou, D.; Dimick-Gray, S.; Mansky, L.M.; Patterson, S.E. Anti-HIV-1 activity of resveratrol derivatives and synergistic inhibition of HIV-1 by the combination of resveratrol and decitabine. Bioorg. Med. Chem. Lett. 2012, 22, 6642–6646. [Google Scholar] [CrossRef] [Green Version]
- Heredia, A.; Davis, C.; Amin, M.N.; Le, N.M.; Wainberg, M.A.; Oliveira, M.; Deeks, S.G.; Wang, L.-X.; Redfield, R.R. Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. AIDS 2014, 28, 317–323. [Google Scholar] [CrossRef] [Green Version]
- Chan, C.N.; Trinité, B.; Levy, D.N. Potent Inhibition of HIV-1 Replication in Resting CD4 T Cells by Resveratrol and Pterostilbene. Antimicrob. Agents Chemother. 2017, 61. [Google Scholar] [CrossRef] [Green Version]
- Zhang, L.; Yuanyuan, L.; Zhiwen, G.; Yuyue, W.; Yun, J.; Jing, S.; Xiaopeng, X.; Lirong, Z. Resveratrol inhibits enterovirus 71 replication and pro-inflammatory cytokine secretion in rhabdosarcoma cells through blocking IKKs/NF-κB signaling pathway. PLoS ONE 2015, 10, e0116879. [Google Scholar] [CrossRef] [Green Version]
- Du, N.; Li, X.; Bao, W.; Wang, B.; Xu, G.; Wang, F. Resveratrol-loaded nanoparticles inhibit enterovirus 71 replication through the oxidative stress-mediated ERS/autophagy pathway. Int. J. Mol. Med. 2019, 44, 737–749. [Google Scholar] [CrossRef]
- Nakamura, M.; Saito, H.; Ikeda, M.; Hokari, R.; Kato, N.; Hibi, T.; Miura, S. An antioxidant resveratrol significantly enhanced replication of hepatitis C virus. World J. Gastroenterol. 2010, 16, 184–192. [Google Scholar] [CrossRef]
- Long, X.; Li, S.; Xie, J.; Li, W.; Zang, N.; Ren, L.; Deng, Y.; Xie, X.; Wang, L.; Fu, Z.; et al. MMP-12-mediated by SARM-TRIF signaling pathway contributes to IFN-γ-independent airway inflammation and AHR post RSV infection in nude mice. Respir. Res. 2015, 16, 11. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kapadia, G.J.; Azuine, M.A.; Tokudab, H.; Takasakic, M.; Mukainakab, T.; Konoshimac, T.; Nishinob, H. Chemopreventive effect of resveratrol, sesamol, sesame oil and sunflower oil in the Epstein-Barr virus early antigen activation assay and the mouse skin two-stage carcinogenesis. Pharmacol. Res. 2002, 45, 499–505. [Google Scholar] [CrossRef] [PubMed]
- De Leo, A.; Arena, G.; Lacanna, E.; Oliviero, G.; Colavita, F.; Mattia, E. Resveratrol inhibits Epstein Barr Virus lytic cycle in Burkitt’s lymphoma cells by affecting multiple molecular targets. Antivir. Res. 2012, 96, 196–202. [Google Scholar] [CrossRef] [PubMed]
- Faith, S.A.; Sweet, T.J.; Bailey, E. Resveratrol suppresses nuclear factor-kappaB in herpes simplex virus infected cells. Antivir. Res. 2006, 72, 242–251. [Google Scholar] [CrossRef] [PubMed]
- Han, Y.S.; Quashie, P.K.; Mesplède, T. A resveratrol analog termed 3,3′,4,4′,5,5′-hexahydroxy-trans-stilbene is a potent HIV-1 inhibitor. J. Med. Virol. 2015, 87, 2054–2060. [Google Scholar] [CrossRef] [PubMed]
- Lin, S.C.; Ho, C.T.; Chou, W.H. Effective inhibition of MERS-CoV infection by resveratrol. BMC Infect. Dis. 2017, 17, 144. [Google Scholar] [CrossRef] [Green Version]
- Horne, J.R.; Vohl, M.C. Biological plausibility for interactions between dietary fat, resveratrol, ACE2, and SARS-CoV illness severity. Am. J. Physiol. Endocrinol. Metab. 2020, 318, E830–E833. [Google Scholar] [CrossRef] [Green Version]
- Marinella, M.A. Indomethacin and resveratrol as potential treatment adjuncts for SARS-CoV-2/COVID-19. Int. J. Clin. Pract. 2020, e13535. [Google Scholar] [CrossRef]
- Huang, C.; Wang, L.; Li, X.; Ren, L.; Zhao, J.; Hu, L.; Zhang, L. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 395, 497–506. [Google Scholar] [CrossRef] [Green Version]
- AlGhatrif, M.; Cingolani, O.; Lakatta, E.G. The Dilemma of Coronavirus Disease 2019, Aging, and Cardiovascular Disease: Insights From Cardiovascular Aging Science. JAMA Cardiol. 2020, 5, 747–748. [Google Scholar] [CrossRef] [Green Version]
- Campagna, M.; Rivas, C. Antiviral activity of resveratrol. Biochem. Soc. Trans. 2010, 38, 50–53. [Google Scholar] [CrossRef] [PubMed]
- Li, Q.; Verma, I.M. NF-kappaB regulation in the immune system. Nat. Rev. Immunol. 2002, 2, 725–734. [Google Scholar] [CrossRef] [PubMed]
- Benedetti, F.; Curreli, S.; Krishnan, S.; Davinelli, S.; Cocchi, F.; Scapagnini, G.; Gallo, R.C.; Zella, D. Anti-inflammatory effects of H2S during acute bacterial infection: A review. J. Transl. Med. 2017, 15, 100. [Google Scholar] [CrossRef] [PubMed]
- Benedetti, F. Sulfur compounds block MCP-1 production by Mycoplasma fermentans-infected macrophages through NF-κB inhibition. J. Transl. Med. 2014, 12, 145. [Google Scholar] [CrossRef] [Green Version]
- Hiscott, J.; Kwon, H.; Génin, P. Hostile takeovers: Viral appropriation of the NF-kappaB pathway. J. Clin. Investig. 2001, 107, 143–151. [Google Scholar] [CrossRef]
- Holmes-McNary, M.; Baldwin, A.S., Jr. Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IkappaB kinase. Cancer Res. 2000, 60, 3477–3483. [Google Scholar]
- Kundu, J.K.; Shin, Y.K.; Kim, S.H.; Surh, Y.J. Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-kappaB in mouse skin by blocking IkappaB kinase activity. Carcinogenesis 2006, 27, 1465–1474. [Google Scholar] [CrossRef]
- Manna, S.K.; Mukhopadhyay, A.; Aggarwal, B.B. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: Potential role of reactive oxygen intermediates and lipid peroxidation. J. Immunol. 2000, 164, 6509–6519. [Google Scholar] [CrossRef] [Green Version]
- Santoro, M.G.; Rossi, A.; Amici, C. NF-kappaB and virus infection: Who controls whom. EMBO J. 2003, 22, 2552–2560. [Google Scholar] [CrossRef]
- Nimmerjahn, F.; Diana, D.; Ulrike, D.; Gerd, H.; Alexander, R.; Martin, S.; Louis, M.S.; Andreas, R.; Uta, B.; Georg, W.B.; et al. Active NF-kappaB signalling is a prerequisite for influenza virus infection. J. Gen. Virol. 2004, 85, 2347–2356. [Google Scholar] [CrossRef]
- Goodkin, M.L.; Ting, A.T.; Blaho, J.A. NF-kappaB is required for apoptosis prevention during herpes simplex virus type 1 infection. J. Virol. 2003, 77, 7261–7280. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tomé-Carneiro, J.; Gonzálvez, M.; Larrosa, M.; Yáñez-Gascón, M.J.; García-Almagro, F.J.; Ruiz-Ros, J.A.; Tomás-Barberán, F.A.; García-Conesa, M.T.; Espín, J.C. Grape resveratrol increases serum adiponectin and downregulates inflammatory genes in peripheral blood mononuclear cells: A triple-blind, placebo-controlled, one-year clinical trial in patients with stable coronary artery disease. Cardiovasc. Drugs Ther. 2013, 27, 37–48. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rafe, T.; Shawon, P.A.; Salem, L.; Chowdhury, N.I.; Kabir, F.; Bin Zahur, S.M.; Akhter, R.; Noor, H.B.; Mohib, M.; Sagor, A.T.; et al. Preventive Role of Resveratrol Against Inflammatory Cytokines and Related Diseases. Curr. Pharm. Des. 2019, 25, 1345–1371. [Google Scholar] [CrossRef]
- Ghanim, H.; Sia, C.L.; Abuaysheh, S.; Korzeniewski, K.; Patnaik, P.; Marumganti, A.; Chaudhuri, A.; Dandona, P. An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol. J. Clin. Endocrinol. Metab. 2010, 95, E1–E8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tili, E.; Michaille, J.-J.; Adair, B.; Alder, H.; Limagne, E.; Taccioli, C.; Ferracin, M.; Delmas, D.; Latruffe, N.; Croce, C.M. Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD. Carcinogenesis 2010, 31, 1561–1566. [Google Scholar] [CrossRef] [PubMed]
- Lin, H.-Y.; Tang, H.-Y.; Davis, F.B.; Davis, P.J. Resveratrol and apoptosis. Ann. N. Y. Acad. Sci. 2011, 1215, 79–88. [Google Scholar] [CrossRef]
- Kulkarni, S.S.; Cantó, C. The molecular targets of resveratrol. Biochim. Biophys. Acta 2015, 1852, 1114–1123. [Google Scholar] [CrossRef] [Green Version]
- Colin, D.; Limagne, E.; Jeanningros, S.; Jacquel, A.; Lizard, G.; Athias, A.; Gambert, P.; Hichami, A.; Latruffe, N.; Solary, E.; et al. Endocytosis of resveratrol via lipid rafts and activation of downstream signaling pathways in cancer cells. Cancer Prev. Res. 2011, 4, 1095–1106. [Google Scholar] [CrossRef] [Green Version]
- Lin, H.Y.; Shih, A.I.; Faith, B.; Tang, H.Y.; Leon, J.M.; James, A.B.; Paul, J.D. Resveratrol induced serine phosphorylation of p53 causes apoptosis in a mutant p53 prostate cancer cell line. J. Urol. 2002, 168, 748–755. [Google Scholar] [CrossRef]
- Shih, A.; Faith, B.; Paul, J.D.; Lin, H.Y. Resveratrol induces apoptosis in thyroid cancer cell lines via a MAPK- and p53-dependent mechanism. J. Clin. Endocrinol. Metab. 2002, 87, 1223–1232. [Google Scholar] [CrossRef]
- Shih, A.; Zhang, S.; Cao, H.J.; Boswell, S.; Wu, Y.-H.; Tang, H.-Y.; Lennartz, M.R.; Davis, F.B.; Davis, P.J.; Lin, H.-Y. Inhibitory effect of epidermal growth factor on resveratrol-induced apoptosis in prostate cancer cells is mediated by protein kinase C-alpha. Mol. Cancer Ther. 2004, 3, 1355–1364. [Google Scholar] [PubMed]
- Zhang, S.; Cao, H.J.; Davis, F.B.; Tang, H.-Y.; Davis, P.J.; Lin, H.-Y. Oestrogen inhibits resveratrol-induced post-translational modification of p53 and apoptosis in breast cancer cells. Br. J. Cancer 2004, 91, 178–185. [Google Scholar] [CrossRef] [Green Version]
- Hsieh, T.C.; Juan, G.; Darzynkiewicz, Z.; Wu, J.M. Resveratrol increases nitric oxide synthase, induces accumulation of p53 and p21(WAF1/CIP1), and suppresses cultured bovine pulmonary artery endothelial cell proliferation by perturbing progression through S and G2. Cancer Res. 1999, 59, 2596–2601. [Google Scholar] [PubMed]
- Carbó, N.; Costelli, P.; Baccino, F.M.; López-Soriano, F.J.; Argilés, J.M. Resveratrol, a natural product present in wine, decreases tumour growth in a rat tumour model. Biochem. Biophys. Res. Commun. 1999, 254, 739–743. [Google Scholar] [CrossRef] [PubMed]
- 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] [PubMed] [Green Version]
- Joerger, A.C.; Fersht, A.R. The p53 Pathway: Origins, Inactivation in Cancer, and Emerging Therapeutic Approaches. Annu. Rev. Biochem. 2016, 85, 375–404. [Google Scholar] [CrossRef]
- Price, N.L.; Gomes, A.P.; Ling, A.J.; Duarte, F.V.; Martin-Montalvo, A.; North, B.J.; Agarwal, B.; Ye, L.; Ramadori, G.; Teodoro, J.S.; et al. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab. 2012, 15, 675–690. [Google Scholar] [CrossRef] [Green Version]
- Maugeri, A.; Barchitta, M.; Mazzone, M.G.; Giuliano, F.; Basile, G.; Agodi, A. Resveratrol Modulates SIRT1 and DNMT Functions and Restores LINE-1 Methylation Levels in ARPE-19 Cells under Oxidative Stress and Inflammation. Int. J. Mol. Sci. 2018, 19, 2118. [Google Scholar] [CrossRef] [Green Version]
- Lee, S.-H.; Lee, J.-H.; Lee, H.-Y.; Min, A.K.-J. Sirtuin signaling in cellular senescence and aging. BMB Rep. 2019, 52, 24–34. [Google Scholar] [CrossRef] [Green Version]
- Lee, S.-H.; Lee, J.-H.; Lee, H.-Y.; Min, A.K.-J. Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J. 2002, 21, 2383–2396. [Google Scholar]
- Luo, J.; Nikolaev, A.Y.; Imai, S.-I.; Chen, D.; Su, F.; Shiloh, A.; Guarente, L.; Gu, W. Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 2001, 107, 137–148. [Google Scholar] [CrossRef] [Green Version]
- Latruffe, N.; Lançon, A.; Frazzi, R.; Aires, V.; Delmas, M.; Michaille, J.-J.; Djouadi, F.; Bastin, J.; Cherkaoui-Malki, M. Exploring new ways of regulation by resveratrol involving miRNAs, with emphasis on inflammation. Ann. N. Y. Acad. Sci. 2015, 1348, 97–106. [Google Scholar] [CrossRef]
- Bai, X.; Yao, L.; Ma, X.; Xu, X. Small Molecules as SIRT Modulators. Mini Rev. Med. Chem. 2018, 18, 1151–1157. [Google Scholar] [CrossRef] [PubMed]
- Pawlowska, E.; Szczepanska, J.; Szatkowska, M.; Blasiak, J. An Interplay between Senescence, Apoptosis and Autophagy in Glioblastoma Multiforme-Role in Pathogenesis and Therapeutic Perspective. Int. J. Mol. Sci. 2018, 19, 889. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ho, Y.; Yang, Y.-C.; Chin, Y.-T.; Chou, S.-Y.; Chen, Y.-R.; Shih, Y.-J.; Whang-Peng, J.; Changou, C.A.; Liu, H.-L.; Lin, S.-J.; et al. Resveratrol inhibits human leiomyoma cell proliferation via crosstalk between integrin αvβ3 and IGF-1R. Food Chem. Toxicol. 2018, 120, 346–355. [Google Scholar] [CrossRef] [PubMed]
- Marel, A.K.; Gérard, L.; Izard, J.C.; Norbert, L.D. Inhibitory effects of trans-resveratrol analogs molecules on the proliferation and the cell cycle progression of human colon tumoral cells. Mol. Nutr. Food Res. 2008, 52, 538–548. [Google Scholar] [CrossRef] [Green Version]
- Colin, D.; Gimazane, A.; Lizard, G.; Izard, J.-C.; Solary, E.; Latruffe, N.; Delmas, D. Effects of resveratrol analogs on cell cycle progression, cell cycle associated proteins and 5fluoro-uracil sensitivity in human derived colon cancer cells. Int. J. Cancer 2009, 124, 2780–2788. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, X.; Xu, Y.; Zhu, B.; Liu, Q.; Yao, Q.; Zhao, G. Resveratrol induces apoptosis in SGC-7901 gastric cancer cells. Oncol. Lett. 2018, 16, 2949–2956. [Google Scholar] [CrossRef]
- Delmas, D.; Passilly-Degrace, P.; Jannin, B.; Malki, M.C.; Latruffe, N. Resveratrol, a chemopreventive agent, disrupts the cell cycle control of human SW480 colorectal tumor cells. Int. J. Mol. Med. 2002, 10, 193–199. [Google Scholar] [CrossRef]
- El-Readi, M.Z.; Eid, S.; Abdelghany, A.A.; Al-Amoudi, H.S.; Efferth, T.; Wink, M. Resveratrol mediated cancer cell apoptosis, and modulation of multidrug resistance proteins and metabolic enzymes. Phytomedicine 2019, 55, 269–281. [Google Scholar] [CrossRef]
- Liu, M.-H.; Lin, X.-L.; Li, J.; He, J.; Tan, T.-P.; Wu, S.-J.; Yu, S.; Chen, L.; Liu, J.; Tian, W.; et al. Resveratrol induces apoptosis through modulation of the Akt/FoxO3a/Bim pathway in HepG2 cells. Mol. Med. Rep. 2016, 13, 1689–1694. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Delmas, D.; Jannin, B.; Malki, M.C.; Latruffe, N. Inhibitory effect of resveratrol on the proliferation of human and rat hepatic derived cell lines. Oncol. Rep. 2000, 7, 847–852. [Google Scholar] [CrossRef] [PubMed]
- Chai, R.; Fu, H.; Zheng, Z.; Liu, T.; Ji, S.; Li, G. Resveratrol inhibits proliferation and migration through SIRT1 mediated post-translational modification of PI3K/AKT signaling in hepatocellular carcinoma cells. Mol. Med. Rep. 2017, 16, 8037–8044. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kabel, A.M.; Atef, A.; Estfanous, R.S. Ameliorative potential of sitagliptin and/or resveratrol on experimentally-induced clear cell renal cell carcinoma. Biomed. Pharmacother. 2018, 97, 667–674. [Google Scholar] [CrossRef] [PubMed]
- Frazzi, R.; Valli, R.; Tamagnini, I.; Casali, B.; Latruffe, N.; Merli, F. Resveratrol-mediated apoptosis of hodgkin lymphoma cells involves SIRT1 inhibition and FOXO3a hyperacetylation. Int. J. Cancer 2013, 132, 1013–1021. [Google Scholar] [CrossRef]
- Frazzi, R.; Guardi, M. Cellular and Molecular Targets of Resveratrol on Lymphoma and Leukemia Cells. Molecules 2017, 22, 885. [Google Scholar] [CrossRef] [Green Version]
- Frazzi, R.; Tigano, M. The multiple mechanisms of cell death triggered by resveratrol in lymphoma and leukemia. Int. J. Mol. Sci. 2014, 15, 4977–4993. [Google Scholar] [CrossRef] [Green Version]
- Castello, L.; Tessitore, L. Resveratrol inhibits cell cycle progression in U937 cells. Oncol. Rep. 2005, 13, 133–137. [Google Scholar]
- Yousef, M.; Vlachogiannis, I.A.; Tsiani, E. Effects of Resveratrol against Lung Cancer: In Vitro and In Vivo Studies. Nutrients 2017, 9, 1231. [Google Scholar] [CrossRef] [Green Version]
- Wang, J.; Li, J.; Cao, N.; Li, Z.; Han, J.; Li, L. Resveratrol, an activator of SIRT1, induces protective autophagy in non-small-cell lung cancer via inhibiting Akt/mTOR and activating p38-MAPK. Onco Targets Ther. 2018, 11, 7777–7786. [Google Scholar] [CrossRef] [Green Version]
- Yuan, L.; Zhang, Y.; Xia, J.; Liu, B.; Zhang, Q.; Liu, J.; Luo, L.; Peng, Z.; Song, Z.; Zhu, R. Resveratrol induces cell cycle arrest via a p53-independent pathway in A549 cells. Mol. Med. Rep. 2015, 11, 2459–2464. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, Y.; Tong, L.; Luo, Y.; Li, X.; Chen, G.; Wang, Y. Resveratrol inhibits the proliferation and induces the apoptosis in ovarian cancer cells via inhibiting glycolysis and targeting AMPK/mTOR signaling pathway. J. Cell Biochem. 2018, 119, 6162–6172. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Yang, S.; Yang, Y.; Liu, T. Resveratrol induces immunogenic cell death of human and murine ovarian carcinoma cells. Infect. Agent Cancer 2019, 14, 27. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aziz, M.H.; Nihal, M.; Fu, V.X.; Jarrard, D.F.; Ahmad, N. Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3′-kinase/Akt pathway and Bcl-2 family proteins. Mol. Cancer Ther. 2006, 5, 1335–1341. [Google Scholar] [CrossRef] [Green Version]
- Singh, S.K.; Saswati, B.; Edward, P.A.; James, W.L.; Rajesh, S. Resveratrol induces cell cycle arrest and apoptosis with docetaxel in prostate cancer cells via a p53/ p21WAF1/CIP1 and p27KIP1 pathway. Oncotarget 2017, 8, 17216–17228. [Google Scholar] [CrossRef] [Green Version]
- Sun, Y.; Zhou, Q.-M.; Lu, Y.-Y.; Zhang, H.; Chen, Q.; Zhao, M.; Shi-Bing, S. 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]
- Pizarro, J.G.; Verdaguer, E.; Ancrenaz, V.; Junyent, F.; Sureda, F.; Pallàs, M.; Folch, J.; Camins, A. Resveratrol inhibits proliferation and promotes apoptosis of neuroblastoma cells: Role of sirtuin 1. Neurochem. Res. 2011, 36, 187–194. [Google Scholar] [CrossRef]
- Liu, L.; Zhang, Y.; Zhu, K.; Song, L.; Tao, M.; Huang, P.; Pan, Y. Resveratrol inhibits glioma cell growth via targeting LRIG1. J. BUON 2018, 23, 403–409. [Google Scholar]
- Cilibrasi, C.; Riva, G.; Romano, G.; Cadamuro, M.; Bazzoni, R.; Butta, V.; Paoletta, L.; Dalprà, L.; Strazzabosco, M.; Lavitrano, M.; et al. Resveratrol Impairs Glioma Stem Cells Proliferation and Motility by Modulating the Wnt Signaling Pathway. PLoS ONE 2017, 12, e0169854. [Google Scholar] [CrossRef] [Green Version]
- Song, Y.; Chen, Y.; Li, Y.; Lyu, X.; Cui, J.; Cheng, Y.; Zheng, T.; Zhao, L.; Zhao, G. Resveratrol Suppresses Epithelial-Mesenchymal Transition in GBM by Regulating Smad-Dependent Signaling. Biomed Res. Int. 2019, 2019, 1321973. [Google Scholar] [CrossRef] [Green Version]
- Zheng, T.; Feng, H.; Liu, L.; Peng, J.; Xiao, H.; Yu, T.; Zhou, Z.; Li, Y.; Zhang, Y.; Bai, X.; et al. Enhanced antiproliferative effect of resveratrol in head and neck squamous cell carcinoma using GE11 peptide conjugated liposome. Int. J. Mol. Med. 2019, 43, 1635–1642. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, M.; Zhou, X.; Zhou, K. Resveratrol inhibits human nasopharyngeal carcinoma cell growth via blocking pAkt/p70S6K signaling pathways. Int. J. Mol. Med. 2013, 31, 621–627. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, G.; Xia, H.; Zhang, Z.-G.; Yu, H. Resveratrol in management of bone and spinal cancers. Nat. Prod. Res. 2019, 33, 516–526. [Google Scholar] [CrossRef] [PubMed]
- Zhao, H.; Han, L.; Jian, Y.; Ma, Y.; Yan, W.; Chen, X.; Xu, H.; Li, L. Resveratrol induces apoptosis in human melanoma cell through negatively regulating Erk/PKM2/Bcl-2 axis. Onco Targets Ther. 2018, 11, 8995–9006. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Baarine, M.; Thandapilly, S.J.; Louis, X.L.; Mazué, F.; Yu, L.; Delmas, D.; Netticadan, T.; Lizard, G.; Latruffe, N. Pro-apoptotic versus anti-apoptotic properties of dietary resveratrol on tumoral and normal cardiac cells. Genes Nutr. 2011, 6, 161–169. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jang, M.; Cai, L.; Udeani, G.O.; Slowing, K.V.; Thomas, C.F.; Beecher, C.W.W.; Fong, H.H.S.; 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. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Takashina, M.; Inoue, S.; Tomihara, K.; Tomita, K.; Hattori, K.; Zhao, Q.-L.; Suzuki, T.; Noguchi, M.; Ohashi, W.; Hattori, Y. Different effect of resveratrol to induction of apoptosis depending on the type of human cancer cells. Int. J. Oncol. 2017, 50, 787–797. [Google Scholar] [CrossRef]
- Trung, L.Q.; Espinoza, J.L.; Takami, A.; Nakao, S. Resveratrol induces cell cycle arrest and apoptosis in malignant NK cells via JAK2/STAT3 pathway inhibition. PLoS ONE 2013, 8, e55183. [Google Scholar] [CrossRef]
- Trung, L.Q.; Espinoza, J.L.; An, D.T.; Viet, N.H.; Shimoda, K.; Nakao, S. Resveratrol selectively induces apoptosis in malignant cells with the JAK2V617F mutation by inhibiting the JAK2 pathway. Mol. Nutr. Food Res. 2015, 59, 2143–2154. [Google Scholar] [CrossRef]
- Shukla, Y.; Singh, R. Resveratrol and cellular mechanisms of cancer prevention. Ann. N. Y. Acad. Sci. 2011, 1215, 1–8. [Google Scholar] [CrossRef]
- Vervandier-Fasseur, D.; Latruffe, N. The Potential Use of Resveratrol for Cancer Prevention. Molecules 2019, 24, 4506. [Google Scholar] [CrossRef] [Green Version]
- Rauf, A.; Imran, M.; Butt, M.S.; Nadeem, M.; Peters, D.G.; Mubarak, M.S. Resveratrol as an anti-cancer agent: A review. Crit. Rev. Food Sci. Nutr. 2018, 58, 1428–1447. [Google Scholar] [CrossRef]
- Rius, S.B.; Ametller, E.; Fuster, G.; Olivan, M.; Raab, V.; Argilés, J.M.; López-Soriano, F.J. Resveratrol, a natural diphenol, reduces metastatic growth in an experimental cancer model. Cancer Lett. 2007, 245, 144–148. [Google Scholar]
- Singh, A.P.; Singh, R.; Verma, S.S.; Rai, V.; Kaschula, C.H.; Maiti, P.; Gupta, S.C. Health benefits of resveratrol: Evidence from clinical studies. Med. Res. Rev. 2019, 39, 1851–1891. [Google Scholar] [CrossRef] [PubMed]
- Howells, L.M.; Berry, D.P.; Elliott, P.J.; Jacobson, E.W.; Hoffmann, E.; Hegarty, B.; Brown, K.; Steward, W.P.; Gescher, A.J. Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases--safety, pharmacokinetics, and pharmacodynamics. Cancer Prev. Res. 2011, 4, 1419–1425. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brown, V.A.; Patel, K.R.; Viskaduraki, M.; Crowell, J.A.; Perloff, M.; Booth, T.D.; Vasilinin, G.; Sen, A.; Schinas, A.M.; Piccirilli, G.; et al. Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: Safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res. 2010, 70, 9003–9011. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Patel, K.R.; Brown, V.A.; Jones, D.J.L.; Britton, R.G.; Hemingway, D.; Miller, A.S.; West, K.P.; Booth, T.D.; Perloff, M.; Crowell, J.A.; et al. Clinical Pharmacology of Resveratrol and Its Metabolites in Colorectal Cancer Patients. Cancer Res. 2010, 70, 7392. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Honari, M.; Shafabakhsh, R.; Reiter, R.J.; Mirzaei, H.; Asemi, Z. Resveratrol is a promising agent for colorectal cancer prevention and treatment: Focus on molecular mechanisms. Cancer Cell Int. 2019, 19, 180. [Google Scholar] [CrossRef] [Green Version]
- Ke, J.; Yang, Y.; Che, Q.; Jiang, F.; Wang, H.; Chen, Z.; Zhu, M.; Tong, H.; Zhang, H.; Yan, X.; et al. Prostaglandin E2 (PGE2) promotes proliferation and invasion by enhancing SUMO-1 activity via EP4 receptor in endometrial cancer. Tumour Biol. 2016, 37, 12203–12211. [Google Scholar] [CrossRef] [Green Version]
- Zhu, W.; Qin, W.; Zhang, K.; Rottinghaus, G.E.; Chen, Y.-C.; Kliethermes, B.; Sauter, E.R. Trans-resveratrol alters mammary promoter hypermethylation in women at increased risk for breast cancer. Nutr. Cancer 2012, 64, 393–400. [Google Scholar] [CrossRef] [Green Version]
- Delmas, D.; Lancon, A.; Colin, D.; Jannin, B.; Latruffe, N. Resveratrol as a chemopreventive agent: A promising molecule for fighting cancer. Curr. Drug Targets 2006, 7, 423–442. [Google Scholar] [CrossRef]
- Davinelli, S.; Sapere, N.; Visentin, M.; Zella, D.; Scapagnini, G. Enhancement of mitochondrial biogenesis with polyphenols: Combined effects of resveratrol and equol in human endothelial cells. Immun. Ageing 2013, 10, 1–5. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abraham, S.K.; Khandelwal, N.; Hintzsche, H.; Stopper, H. Antigenotoxic effects of resveratrol: Assessment of in vitro and in vivo response. Mutagenesis 2016, 31, 27–33. [Google Scholar] [PubMed] [Green Version]
- Tili, E.; Michaille, J.-J.; Alder, H.; Volinia, S.; Delmas, D.; Latruffe, N.; Croce, C.M. Resveratrol modulates the levels of microRNAs targeting genes encoding tumor-suppressors and effectors of TGFβ signaling pathway in SW480 cells. Biochem. Pharmacol. 2010, 80, 2057–2065. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alghetaa, H.; Mohammed, A.; Sultan, M.; Busbee, P.; Murphy, A.; Chatterjee, S.; Nagarkatti, M.; Nagarkatti, P. Resveratrol protects mice against SEB-induced acute lung injury and mortality by miR-193a modulation that targets TGF-β signalling. J. Cell Mol. Med. 2018, 22, 2644–2655. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Y.; Lu, Y.; Ong’Achwa, M.J.; Ge, L.; Qian, Y.; Chen, L.; Machuki, J.O.; Li, F.; Wei, H.; Zhang, C.; et al. Resveratrol Inhibits the TGF-β1-Induced Proliferation of Cardiac Fibroblasts and Collagen Secretion by Downregulating miR-17 in Rat. Biomed Res. Int. 2018, 2018, 8730593. [Google Scholar] [CrossRef] [Green Version]
- McCubrey, J.A.; Lertpiriyapong, K.; Steelman, L.S.; Abrams, S.L.; Yang, L.V.; Murata, R.M.; Rosalen, P.L.; Scalisi, A.; Neri, L.M.; Cocco, L.; et al. Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs. Aging 2017, 9, 1477–1536. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sehgal, S.; Baker, A.; Vezina, C. Rapamycin (AY-22, 989), A New Antifungal Antibiotic. J. Antibiot. 1975, 28, 727–732. [Google Scholar] [CrossRef] [Green Version]
- Blagosklonny, M.V. Fasting and rapamycin: Diabetes versus benevolent glucose intolerance. Cell Death Dis. 2019, 10, 607. [Google Scholar] [CrossRef] [Green Version]
- Araki, K.; Turner, A.P.; Shaffer, V.O.; Gangappa, S.; Keller, S.A.; Bachmann, M.F.; Larsen, C.P.; Ahmed, R. mTOR regulates memory CD8 T-cell differentiation. Nature 2009, 460, 108–112. [Google Scholar] [CrossRef] [Green Version]
- Saso, W.; Tsukuda, S.; Ohashi, H.; Fukano, K.; Morishita, R.; Matsunaga, S.; Ohki, M.; Ryo, A.; Park, S.-Y.; Suzuki, R.; et al. A new strategy to identify hepatitis B virus entry inhibitors by AlphaScreen technology targeting the envelope-receptor interaction. Biochem. Biophys. Res. Commun. 2018, 501, 374–379. [Google Scholar] [CrossRef] [PubMed]
- Adamson, A.L.; Le, B.T.; Siedenburg, B.D. Inhibition of mTORC1 inhibits lytic replication of Epstein-Barr virus in a cell-type specific manner. Virol. J. 2014, 11, 110. [Google Scholar] [CrossRef] [PubMed]
- Needham, J.; Adamson, A.L. BZLF1 transcript variants in Epstein-Barr virus-positive epithelial cell lines. Virus Genes 2019, 55, 779–785. [Google Scholar] [CrossRef] [PubMed]
- Heredia, A.; Gilliam, B.; Latinovic, O.; Le, N.; Bamba, D.; DeVico, A.; Melikyan, G.B.; Gallo, R.C.; Redfield, R.R. Rapamycin reduces CCR5 density levels on CD4 T cells, and this effect results in potentiation of enfuvirtide (T-20) against R5 strains of human immunodeficiency virus type 1 in vitro. Antimicrob. Agents Chemother. 2007, 51, 2489–2496. [Google Scholar] [CrossRef] [Green Version]
- Heredia, A.; Latinovic, O.; Gallo, R.C.; Melikyan, G.; Reitz, M.; Le, N.; Redfield, R.R. Reduction of CCR5 with low-dose rapamycin enhances the antiviral activity of vicriviroc against both sensitive and drug-resistant HIV-1. Proc. Natl. Acad. Sci. USA 2008, 105, 20476–20481. [Google Scholar] [CrossRef] [Green Version]
- Latinovic, O.S.; Neal, L.M.; Tagaya, Y.; Heredia, A.; Medina-Moreno, M.S.; Zapata, J.C.; Reitz, M.; Bryant, J.; Redfield, R.R. Suppression of Active HIV-1 Infection in CD34(+) Hematopoietic Humanized NSG Mice by a Combination of Combined Antiretroviral Therapy and CCR5 Targeting Drugs. AIDS Res. Hum. Retrovir. 2019, 35, 718–728. [Google Scholar] [CrossRef]
- Weichseldorfer, M.; Yvonne, A.; Alonso, H.; Yutaka, T.; Francesca, B.; Davide, Z.; Marvin, R.; Fabio, R.; Olga, S.L. Anti-HIV Activity of Standard cART in Primary Cells Is Intensified by CCR5-Targeting Drugs. AIDS Res. Hum. Retrovir. 2020, 36, 835–841. [Google Scholar] [CrossRef]
- Martin, A.R.; Pollack, R.A.; Capoferri, A.A.; Ambinder, R.F.; Durand, C.M.; Siliciano, R.F. Rapamycin-mediated mTOR inhibition uncouples HIV-1 latency reversal from cytokine-associated toxicity. J. Clin. Investig. 2017, 127, 651–656. [Google Scholar] [CrossRef] [Green Version]
- Comins, C.; Simpson, G.R.; Rogers, W.; Relph, K.; Harrington, K.; A Melcher, A.; Roulstone, V.; Kyula, J.; Pandha, H. Synergistic antitumour effects of rapamycin and oncolytic reovirus. Cancer Gene Ther. 2018, 25, 148–160. [Google Scholar] [CrossRef]
- Foretz, M.; Guigas, B.; Bertrand, L.; Pollak, M.; Viollet, B. Metformin: From mechanisms of action to therapies. Cell Metab. 2014, 20, 953–966. [Google Scholar] [CrossRef] [Green Version]
- Santos, S.; Marín, A.; Serra-Batlles, J.; De La Rosa, D.; Solanes, I.; Pomares, X.; López-Sánchez, M.; Muñoz-Esquerre, M.; Miravitlles, M. Treatment of patients with COPD and recurrent exacerbations: The role of infection and inflammation. Int. J. Chron. Obstruct. Pulmon. Dis. 2016, 11, 515–525. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pryor, R.; Cabreiro, F. Repurposing metformin: An old drug with new tricks in its binding pockets. Biochem. J. 2015, 471, 307–322. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kalender, A.; Selvaraj, A.; Kim, S.Y.; Gulati, P.; Brûlé, S.; Viollet, B.; Kemp, B.E.; Bardeesy, N.; Dennis, P.; Schlager, J.J.; et al. Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab. 2010, 11, 390–401. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Madiraju, A.K.; Erion, D.M.; Rahimi, Y.; Zhang, X.-M.; Braddock, D.T.; Albright, R.A.; Prigaro, B.J.; Wood, J.L.; Bhanot, S.; Macdonald, M.J.; et al. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature 2014, 510, 542–546. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bridges, H.R.; Sirviö, V.A.; Agip, A.-N.A.; Hirst, J. Molecular features of biguanides required for targeting of mitochondrial respiratory complex I and activation of AMP-kinase. BMC Biol. 2016, 14, 1–11. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bridges, H.R.; Jones, A.J.Y.; Pollak, M.N.; Hirst, J. Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria. Biochem. J. 2014, 462, 475–487. [Google Scholar] [CrossRef] [Green Version]
- Howell, J.J.; Hellberg, K.; Turner, M.; Talbott, G.; Kolar, M.J.; Ross, D.V.; Hoxhaj, G.; Saghatelian, A.; Shaw, R.J.; Manning, B.D. Metformin inhibits hepatic mTORC1 signaling via dose-dependent mechanisms involving AMPK and the TSC complex. Cell Metab. 2017, 25, 463–471. [Google Scholar] [CrossRef] [Green Version]
- Gui, D.Y.; Sullivan, L.B.; Luengo, A.; Hosios, A.M.; Bush, L.N.; Gitego, N.; Davidson, S.M.; Freinkman, E.; Thomas, C.J.; Heiden, M.G.V. Environment dictates dependence on mitochondrial complex I for NAD+ and aspartate production and determines cancer cell sensitivity to metformin. Cell Metab. 2016, 24, 716–727. [Google Scholar] [CrossRef] [Green Version]
- Shaw, R.J.; Lamia, K.A.; Vasquez, D.; Koo, S.-H.; Bardeesy, N.; Depinho, R.A.; Montminy, M.; Cantley, L.C. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 2005, 310, 1642–1646. [Google Scholar] [CrossRef] [Green Version]
- Zhou, G.; Myers, R.; Li, Y.; Chen, X.; Shen, J.; Fenyk-Melody, M.; Wu, J.; Ventre, T.D.; Fujii, N.; Musi, N. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Investig. 2001, 108, 1167–1174. [Google Scholar] [CrossRef]
- Rena, G.; Hardie, D.G.; Pearson, E.R. The mechanisms of action of metformin. Diabetologia 2017, 60, 1577–1585. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Arrieta, O.; Varela-Santoyo, E.; Soto-Perez-De-Celis, E.; Sánchez-Reyes, R.; De La Torre-Vallejo, M.; Muñiz-Hernández, S.; Cardona, A.F. Metformin use and its effect on survival in diabetic patients with advanced non-small cell lung cancer. BMC Cancer 2016, 16, 633. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sayed, R.; Saad, A.S.; El Wakeel, L.; Elkholy, E.; Badary, O. Metformin Addition to Chemotherapy in Stage IV Non-Small Cell Lung Cancer: An Open Label Randomized Controlled Study. Asian Pac. J. Cancer Prev. 2015, 16, 6621–6626. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morgillo, F.; Fasano, M.; Della Corte, C.M.; Sasso, F.C.; Papaccio, F.; Viscardi, G.; Esposito, G.; Di Liello, R.; Normanno, N.; Capuano, A.; et al. Results of the safety run-in part of the METAL (METformin in Advanced Lung cancer) study: A multicentre, open-label phase I-II study of metformin with erlotinib in second-line therapy of patients with stage IV non-small-cell lung cancer. ESMO Open 2017, 2, e000132. [Google Scholar] [CrossRef] [Green Version]
- Wan, G.; Yu, X.; Chen, P.; Wang, X.; Pan, D.; Wang, X.; Li, L.; Cai, X.; Cao, F. Metformin therapy associated with survival benefit in lung cancer patients with diabetes. Oncotarget 2016, 7, 35437–35445. [Google Scholar] [CrossRef] [Green Version]
- Tseng, C.-H. Metformin reduces gastric cancer risk in patients with type 2 diabetes mellitus. Aging 2016, 8, 1636–1649. [Google Scholar] [CrossRef] [Green Version]
- Park, J.W.; Lee, J.H.; Park, Y.; Park, S.J.; Cheon, J.H.; Kim, W.H.; Kim, T.I. Sex-dependent Difference in the effect of metformin on colorectal cancer-specific mortality of Diabetic colorectal cancer patients. World J. Gastroenterol. 2017, 23, 5196. [Google Scholar] [CrossRef]
- Coyle, C.; Cafferty, F.H.; Vale, C.; Langley, R.E. Metformin as an adjuvant treatment for cancer: A systematic review and meta-analysis. Ann. Oncol. 2016, 27, 2184–2195. [Google Scholar] [CrossRef]
- Haring, A.; Murtola, T.J.; Talala, K.; Taari, K.; Tammela, T.L.J.; Auvinen, A. Antidiabetic drug use and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer. Scand. J. Urol. 2017, 51, 5–12. [Google Scholar] [CrossRef]
- He, X.; Esteva, F.J.; Ensor, J.; Hortobagyi, G.N.; Lee, M.-H.; Yeung, S.-C.J. Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer. Ann. Oncol. 2012, 23, 1771–1780. [Google Scholar] [CrossRef]
- Lega, I.C.; Fung, K.; Austin, P.; Lipscombe, L. Metformin and breast cancer stage at diagnosis: A population-based study. Curr. Oncol. 2017, 24, e85–e91. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, K.; Qian, W.; Jiang, Z.; Cheng, L.; Liang, C.; Sun, L.; Zhou, C.; Gao, L.; Lei, M.; Yan, B.; et al. Metformin suppresses cancer initiation and progression in genetic mouse models of pancreatic cancer. Mol. Cancer 2017, 16, 131. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Li, T.; Liu, Z.; Gou, S.; Wang, C. The effect of metformin on survival of patients with pancreatic cancer: A meta-analysis. Sci. Rep. 2017, 7, 5825. [Google Scholar] [CrossRef] [PubMed]
- Christodoulou, M.I.; Scorilas, A. Metformin and Anti-Cancer Therapeutics: Hopes for a More Enhanced Armamentarium Against Human Neoplasias? Curr. Med. Chem. 2017, 24, 14–56. [Google Scholar] [CrossRef]
- Mallik, R.; Chowdhury, T.A. Metformin in cancer. Diabetes Res. Clin. Pract. 2018, 143, 409–419. [Google Scholar] [CrossRef]
- Chen, K.; Li, Y.; Guo, Z.; Zeng, Y.; Zhang, W.; Wang, H. Metformin: Current clinical applications in nondiabetic patients with cancer. Aging 2020, 12, 3993–4009. [Google Scholar] [CrossRef]
- Wu, H.; Esteve, E.; Tremaroli, V.; Khan, M.T.; Caesar, R.; Mannerås-Holm, L.; Ståhlman, M.; Olsson, L.M.; Serino, M.; Planas-Fèlix, M.; et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nature Med. 2017, 23, 850–858. [Google Scholar] [CrossRef]
- Wu, K.; Tian, R.; Huang, J.; Yang, Y.; Dai, J.; Jiang, R.; Zhang, L. Metformin alleviated endotoxemia-induced acute lung injury via restoring AMPK-dependent suppression of mTOR. Chemico-Biol. Interact. 2018, 291, 1–6. [Google Scholar] [CrossRef]
- Brima, W.; Daniel, J.; Syed, F.; Michelle, B.; Mohammad, M.; Joanna, S.; Vanessa, A.; Dazhi, Z.; Irwin, K.; Jeffrey, E.; et al. The brighter (and evolutionarily older) face of the metabolic syndrome: Evidence from Trypanosoma cruzi infection in CD-1 mice. Diabetes Metab. Res. Rev. 2015, 31, 346–359. [Google Scholar] [CrossRef] [Green Version]
- Singhal, A.; Jie, L.; Kumar, P.; Hong, G.S.; Leow, M.K.-S.; Paleja, B.; Tsenova, L.; Kurepina, N.; Chen, J.; Zolezzi, F.; et al. Metformin as adjunct antituberculosis therapy. Sci. Transl. Med. 2014, 6, 263ra159. [Google Scholar] [CrossRef]
- Malik, F.; Syed, F.M.; Ali, H.; Patel, P. Is metformin poised for a second career as an antimicrobial? Diabetes Metab. Res. Rev. 2018, 34, e2975. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xun, Y.-H.; Zhang, J.; Pan, Q.-C.; Mao, R.-C.; Qin, Y.-L.; Liu, H.-Y.; Yu, Y.-S.; Tang, Z.-H.; Lu, M.-J.; Zang, G.-Q. Metformin inhibits hepatitis B virus protein production and replication in human hepatoma cells. J. Viral Hepat. 2014, 21, 597–603. [Google Scholar] [CrossRef] [PubMed]
- Del Campo, J.; García-Valdecasas, M.; Gil-Gómez, A.; Rojas, Á.; Gallego, P.; Ampuero, J.; Gallego-Durán, R.; Pastor, H.; Grande, L.; Padillo, F.J.; et al. Simvastatin and metformin inhibit cell growth in hepatitis C virus infected cells via mTOR increasing PTEN and autophagy. PLoS ONE 2018, 13, e0191805. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- El-Arabey, A.A.; Abdalla, M. Metformin and COVID-19: A novel deal of an old drug. J. Med. Virol. 2020. [Google Scholar] [CrossRef] [PubMed]
- Esam, Z. A proposed mechanism for the possible therapeutic potential of Metformin in COVID-19. Diabetes Res. Clin. Pract. 2020, 167, 108282. [Google Scholar] [CrossRef] [PubMed]
- Menendez, J.A. Metformin and SARS-CoV-2: Mechanistic lessons on air pollution to weather the cytokine/thrombotic storm in COVID-19. Aging 2020, 12, 8760–8765. [Google Scholar] [CrossRef] [PubMed]
- Blanco-Melo, D.; Payant, B.E.; Liu, W.C.; Hoagland, D.; Oishi, K.; Panis, M. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell 2020, 181, 1036–1045.e9. [Google Scholar] [CrossRef]
- Kim, J.; You, Y.-J. Regulation of organelle function by metformin. IUBMB Life 2017, 69, 459–469. [Google Scholar] [CrossRef] [Green Version]
- Zhang, C.-S.; Li, M.; Ma, T.; Zong, Y.; Cui, J.; Feng, J.-W.; Wu, Y.-Q.; Lin, S.-Y.; Lin, S.-C. Metformin Activates AMPK through the Lysosomal Pathway. Cell Metab. 2016, 24, 521–522. [Google Scholar] [CrossRef] [Green Version]
Virus | Antiviral Effects |
---|---|
Influenza Virus | Block of nuclear-cytoplasmic translocation in decreased expression [31]. |
Respiratory syncytial virus (RPSV) | Reduced inflammation and levels IFN-γ and TLR3; inhibition of TRIF signaling, induction of M2R [35,36]; decreased production of IL-6 and TBK1 [34]; increased expression of SARM and decreased expression of MMP-12 and TRIF leading to decreased IFN-γ expression and AHR [33,51]; reduced levels of NGF [36]; increased levels of TNF-α, IFN-γ, and IL-2 in infected mice [32]. |
Varicella Zoster virus | Decreased synthesis of IE 62 [38]. |
Epstein-Barr virus (EBV) | Inhibition of EBV early antigen and reduced papilloma production in mouse [52]; inhibition of EBV lytic cycle resulting in reduced production of viral particles [40]; inhibition of protein synthesis, reduction in ROS production, and inhibition of transcription factors NF-κB and AP1 [53]; prevention of EBV-mediated transformation of human B-cells [39]. |
Herpes simplex virus (HSV-1 and HSV-2) | Decreased production of early viral protein ICP-4 and reduced production of viral particles; prevention of virus reactivation in latently infected neuron cells [43]; suppression of the development of cutaneous lesions in abraded skin infected with HSV-1 [44]; prevention of the development of vaginal lesions in mice infected with HSV-2 and HSV-1, with reduced mortality rate [42]; inhibition of the expression of immediate-early, early, and late HSV genes and viral DNA synthesis [41,54]. |
Human immunodeficiency virus (HIV) | Resveratrol, decitabine and 15 other derivatives of resveratrol were potent antiviral drugs [45]: inhibition of DNA synthesis [46]; block of HIV-1 infection in resting CD4 T cells; 3,3′,4,4′,5,5′-hexahydroxy-trans-stilbene (M8) showed potent anti-HIV activity [55]. |
Enterovirus 71 (EV 71) | Inhibition of viral protein 1 (VP1) synthesis and phosphorylation of proinflammatory cytokines in Rhabdomyosarcoma cell line [48]. |
MERS-CoV | Inhibition of MERS-CoV infection; downregulation of apoptosis induced by MERS-CoV in vitro [56]. |
SARS-CoV-2 | Upregulation of ACE-2 [57]; decreased high levels of circulating cytokines such as IL-6 and TNF-α, upregulated following SARS-CoV-2 infection [58]. |
Virus | Antiviral Effects |
---|---|
Acute lymphocytic choriomeningitis virus | Enhanced amount and quantity/function of virus specific CD8+ T cells [150]. |
Hepatitis B virus (HBV) | Inhibition of the interaction between LHBs and NCTP and consequent infection reduction [151]. |
Epstein Bar Virus (EBV) | Reduced levels of BZLF1 transcripts [152]; altered production of viral transcripts [153]. |
Human immunodeficiency virus (HIV) | Reduced CCR5 levels and improvement of antiviral compound T20 [154,155,156,157]. |
Bacterium/Virus | Effects |
---|---|
T. cruzi, T. spiralis, S. aureus, P. aeruginosa | Antibacterial [189,190,191] |
Hepatitis B Virus (HBV) | Reduced HBsAg expression and viral replication [192] |
Hepatitis C Virus (HCV) | In combination with simvastatin, it was observed reduction of mTOR and PTEN levels, and upregulation of p62, LC3BII and caspase 3 in human primary hepatocytes in vitro [193] |
SARS-CoV-2 | Reduction of IL-6 levels, increase of cellular pH levels and reduction of viral replication [194,195,196,197,198,199] |
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Benedetti, F.; Sorrenti, V.; Buriani, A.; Fortinguerra, S.; Scapagnini, G.; Zella, D. Resveratrol, Rapamycin and Metformin as Modulators of Antiviral Pathways. Viruses 2020, 12, 1458. https://doi.org/10.3390/v12121458
Benedetti F, Sorrenti V, Buriani A, Fortinguerra S, Scapagnini G, Zella D. Resveratrol, Rapamycin and Metformin as Modulators of Antiviral Pathways. Viruses. 2020; 12(12):1458. https://doi.org/10.3390/v12121458
Chicago/Turabian StyleBenedetti, Francesca, Vincenzo Sorrenti, Alessandro Buriani, Stefano Fortinguerra, Giovanni Scapagnini, and Davide Zella. 2020. "Resveratrol, Rapamycin and Metformin as Modulators of Antiviral Pathways" Viruses 12, no. 12: 1458. https://doi.org/10.3390/v12121458