Sirtuin-3 (SIRT3) and the Hallmarks of Cancer

Genes and Cancer

Volumn 4, Issue 3-4, 2013, Pages 164-171

  Alhazzazi, Turki Y ^a,b   Kamarajan, Pachiyappan ^b   Verdin, Eric ^c   Kapila, Yvonne L ^b  

^a KING ABDULAZIZ UNIVERSITY   (Saudi Arabia)

^b UNIVERSITY OF MICHIGAN SCHOOL OF DENTISTRY   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

anoikis; cancer; SIRT3; sirtuin 3; sirtuins; tumor promoter; tumor suppressor

Indexed keywords

CARCINOGEN; HYPOXIA INDUCIBLE FACTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; REACTIVE OXYGEN METABOLITE; SIRTUIN 2; SIRTUIN 3; TRANSCRIPTION FACTOR FKHRL1;

ANOIKIS; APOPTOSIS; ARTICLE; CANCER CELL; CANCER GROWTH; CANCER INHIBITION; CANCER THERAPY; CARCINOGENESIS; CELL DEATH; CELL DIVISION; CELL METABOLISM; CELL PROLIFERATION; CELL STRESS; CELL SURVIVAL; CELLULAR DISTRIBUTION; CHROMOSOMAL INSTABILITY; CYTOLOGY; DISEASE MARKER; DNA DAMAGE; DNA MODIFICATION; DRUG TARGETING; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME REGULATION; GENE INACTIVATION; GENE MUTATION; GENOMIC INSTABILITY; HISTONE MODIFICATION; HUMAN; IMMUNE RESPONSE; INFLAMMATION; INTRACELLULAR SIGNALING; LONG TERM EXPOSURE; MALIGNANT NEOPLASTIC DISEASE; METASTASIS; MOLECULAR MECHANICS; NONHUMAN; ONCOGENE; OXIDATIVE STRESS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN LOCALIZATION; TUMOR INVASION; TUMOR SUPPRESSOR GENE; TUMOR VASCULARIZATION;

EID: 84887450037     PISSN: 19476019     EISSN: 19476027     Source Type: Journal    
DOI: 10.1177/1947601913486351     Document Type: Article

References (122)

1. HoyertDonna L.XuJiaquan. 2012. Deaths: Preliminary Data for 2011. National Vital Statistics Reports, Vol. 61, No 6, October10, 2012. Available from: http://www.cdc.gov/nchs/fastats/lcod.htm.
2. McGuinness D,McGuinness DH,McCaul JA,Shiels PG.Sirtuins, bioageing, and cancer.J Aging Res. 2011;2011:235754.
3. Saunders LR,Verdin E.Sirtuins: critical regulators at the crossroads between cancer and aging.Oncogene. 2007;26:5489-504.
4. Martinez-Pastor B,Mostoslavsky R.Sirtuins, metabolism, and cancer.Front Pharmacol. 2012;3:22.
5. Haigis MC,Guarente LP.Mammalian sirtuins: emerging roles in physiology, aging, and calorie restriction.Genes Dev. 2006;20:2913-21.
6. Fischle W,Kiermer V,Dequiedt F,Verdin E.The emerging role of class II histone deacetylases.Biochem Cell Biol. 2001;79:337-48.
7. Alhazzazi TY,Kamarajan P,Verdin E,Kapila YL.SIRT3 and cancer: tumor promoter or suppressor?.Biochim Biophys Acta. 2011;1816:80-8.
8. Hanahan D,Weinberg RA.The hallmarks of cancer.Cell. 2000;100:57-70.
9. Hanahan D,Weinberg RA.Hallmarks of cancer: the next generation.Cell. 2011;144:646-74.
10. Bakhoum SF,Compton DA.Chromosomal instability and cancer: a complex relationship with therapeutic potential.J Clin Invest. 2012;122:1138-43.
11. Floor SL,Dumont JE,Maenhaut C,Raspe E.Hallmarks of cancer: of all cancer cells, all the time?.Trends Mol Med. 2012;18:509-15.
12. Negrini S,Gorgoulis VG,Halazonetis TD.Genomic instability: an evolving hallmark of cancer.Nat Rev Mol Cell Biol. 2010;11:220-8.
13. Knudson AG.Mutation and cancer: statistical study of retinoblastoma.Proc Natl Acad Sci U S A. 1971;68:820-3.
14. Loeb LA,Loeb KR,Anderson JP.Multiple mutations and cancer.Proc Natl Acad Sci U S A. 2003;100:776-81.
15. Loeb LA.Human cancers express mutator phenotypes: origin, consequences and targeting.Nat Rev Cancer. 2011;11:450-7.
16. Choi S,Myers JN.Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy.J Dent Res. 2008;87:14-32.
17. Wang RH,Sengupta K,Li C,et al.Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice.Cancer Cell. 2008;14:312-23.
18. Hiratsuka M,Inoue T,Toda T,et al.Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene.Biochem Biophys Res Commun. 2003;309:558-66.
19. Dryden SC,Nahhas FA,Nowak JE,Goustin AS,Tainsky MA.Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle.Mol Cell Biol. 2003;23:3173-85.
20. Inoue T,Hiratsuka M,Osaki M,et al.SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress.Oncogene. 2007;26:945-57.
21. Mostoslavsky R,Chua KF,Lombard DB,et al.Genomic instability and aging-like phenotype in the absence of mammalian SIRT6.Cell. 2006;124:315-29.
22. Michishita E,Park JY,Burneskis JM,Barrett JC,Horikawa I.Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins.Mol Biol Cell. 2005;16:4623-35.
23. Lombard DB,Alt FW,Cheng HL,et al.Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation.Mol Cell Biol. 2007;27:8807-14.
24. Schwer B,North BJ,Frye RA,Ott M,Verdin E.The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase.J Cell Biol. 2002;158:647-57.
25. Cooper HM,Spelbrink JN.The human Sirt3 protein deacetylase is exclusively mitochondrial.Biochem J. 2008;411:279-85.
26. Onyango P,Celic I,McCaffery JM,Boeke JD,Feinberg AP.SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria.Proc Natl Acad Sci U S A. 2002;99:13653-8.
27. Shi T,Wang F,Stieren E,Tong Q.SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes.J Biol Chem. 2005;280:13560-7.
28. Jin L,Galonek H,Israelian K,et al.Biochemical characterization, localization, and tissue distribution of the longer form of mouse SIRT3.Protein Sci. 2009;18:514-25.
29. Bao J,Lu Z,Joseph JJ,et al.Characterization of the murine SIRT3 mitochondrial localization sequence and comparison of mitochondrial enrichment and deacetylase activity of long and short SIRT3 isoforms.J Cell Biochem. 2010;110:238-47.
30. Ahn BH,Kim HS,Song S,et al.A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis.Proc Natl Acad Sci U S A. 2008;105:14447-52.
31. Kim HS,Patel K,Muldoon-Jacobs K,et al.SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress.Cancer Cell. 2010;17:41-52.
32. Tao R,Coleman MC,Pennington JD,et al.Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress.Mol Cell. 2010;40:893-904.
33. Qiu X,Brown K,Hirschey MD,Verdin E,Chen D.Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation.Cell Metab. 2010;12:662-7.
34. Tudek B,Winczura A,Janik J,et al.Involvement of oxidatively damaged DNA and repair in cancer development and aging.Am J Transl Res. 2010;2:254-84.
35. Scher MB,Vaquero A,Reinberg D.SirT3 is a nuclear NAD+-dependent histone deacetylase that translocates to the mitochondria upon cellular stress.Genes Dev. 2007;21:920-8.
36. Harley CB,Futcher AB,Greider CW.Telomeres shorten during ageing of human fibroblasts.Nature. 1990;345:458-60.
37. Stewart SA,Weinberg RA.Telomerase and human tumorigenesis.Semin Cancer Biol. 2000;10:399-406.
38. Shay JW,Wright WE.Telomerase therapeutics for cancer: challenges and new directions.Nat Rev Drug Discov. 2006;5:577-84.
39. Mao L,El-Naggar AK,Fan YH,et al.Telomerase activity in head and neck squamous cell carcinoma and adjacent tissues.Cancer Res. 1996;56:5600-4.
40. Chen HH,Yu CH,Wang JT,et al.Expression of human telomerase reverse transcriptase (hTERT) protein is significantly associated with the progression, recurrence and prognosis of oral squamous cell carcinoma in Taiwan.Oral Oncol. 2007;43:122-9.
41. Michishita E,McCord RA,Berber E,et al.SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin.Nature. 2008;452:492-6.
42. Michishita E,McCord RA,Boxer LD,et al.Cell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6.Cell Cycle. 2009;8:2664-6.
43. Narala SR,Allsopp RC,Wells TB,et al.SIRT1 acts as a nutrient-sensitive growth suppressor and its loss is associated with increased AMPK and telomerase activity.Mol Biol Cell. 2008;19:1210-9.
44. Alhazzazi TY,Kamarajan P,Joo N,et al.Sirtuin-3 (SIRT3), a novel potential therapeutic target for oral cancer.Cancer. 2011;117:1670-8.
45. Kamarajan P,Alhazzazi TY,Danciu T,et al.Receptor-interacting protein (RIP) and sirtuin-3 (SIRT3) are on opposite sides of anoikis and tumorigenesis.Cancer. 2012;118:5800-10.
46. Sundaresan NR,Samant SA,Pillai VB,Rajamohan SB,Gupta MP.SIRT3 is a stress responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku-70.Mol Cell Biol. 2008;28:6384-401.
47. Yang H,Yang T,Baur JA,et al.Nutrient-sensitive mitochondrial NAD(+) levels dictate cell survival.Cell. 2007;130:1095-107.
48. Benigni A,Corna D,Zoja C,et al.Disruption of the Ang II type 1 receptor promotes longevity in mice.J Clin Invest. 2009;119:524-30.
49. Sundaresan NR,Gupta M,Kim G,et al.Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice.J Clin Invest. 2009;119:2758-71.
50. Hafner AV,Dai J,Gomes AP,et al.Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy.Aging (Albany NY). 2010;2:914-23.
51. Pillai VB,Sundaresan NR,Kim G,et al.Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway.J Biol Chem. 2010;285:3133-44.
52. Kim SH,Lu HF,Alano CC.Neuronal Sirt3 protects against excitotoxic injury in mouse cortical neuron culture.PLoS One. 2011;6:e14731.
53. Li S,Banck M,Mujtaba S,et al.p53-induced growth arrest is regulated by the mitochondrial SirT3 deacetylase.PLoS One. 2010;5:e10486.
54. Ashraf N,Zino S,Macintyre A,et al.Altered sirtuin expression is associated with node-positive breast cancer.Br J Cancer. 2006;95:1056-61.
55. Wu WS.The signaling mechanism of ROS in tumor progression.Cancer Metastasis Rev. 2006;25:695-705.
56. Behrend L,Henderson G,Zwacka RM.Reactive oxygen species in oncogenic transformation.Biochem Soc Trans. 2003;31:1441-4.
57. Szatrowski TP,Nathan CF.Production of large amounts of hydrogen peroxide by human tumor cells.Cancer Res. 1991;51:794-8.
58. Toyokuni S,Okamoto K,Yodoi J,Hiai H.Persistent oxidative stress in cancer.FEBS Lett. 1995;358:1-3.
59. Fleury C,Mignotte B,Vayssiere JL.Mitochondrial reactive oxygen species in cell death signaling.Biochimie. 2002;84:131-41.
60. Gamaley IA,Klyubin IV.Roles of reactive oxygen species: signaling and regulation of cellular functions.Int Rev Cytol. 1999;188:203-55.
61. Chen CJ,Fu YC,Yu W,Wang W.SIRT3 protects cardiomyocytes from oxidative stress-mediated cell death by activating NF-kappaB.Biochem Biophys Res Commun. 2013;430:798-803.
62. Fu J,Jin J,Cichewicz RH,et al.Trans-(-)-epsilon-viniferin increases mitochondrial sirtuin 3 (SIRT3), activates AMP-activated protein kinase (AMPK), and protects cells in models of Huntington disease.J Biol Chem. 2012;287:24460-72.
63. Semenza GL.Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy.Trends Pharmacol Sci. 2012;33:207-14.
64. Finley LW,Carracedo A,Lee J,et al.SIRT3 opposes reprogramming of cancer cell metabolism through HIF1alpha destabilization.Cancer Cell. 2011;19:416-28.
65. Bell EL,Emerling BM,Ricoult SJ,Guarente L.SirT3 suppresses hypoxia inducible factor 1alpha and tumor growth by inhibiting mitochondrial ROS production.Oncogene. 2011;30:2986-96.
66. Roy SK,Srivastava RK,Shankar S.Inhibition of PI3K/AKT and MAPK/ERK pathways causes activation of FOXO transcription factor, leading to cell cycle arrest and apoptosis in pancreatic cancer.J Mol Signal. 2010;5:10.
67. Joseph EW,Pratilas CA,Poulikakos PI,et al.The RAF inhibitor PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAF-selective manner.Proc Natl Acad Sci U S A. 2010;107:14903-8.
68. Han SS,Yun H,Son DJ,et al.NF-kappaB/STAT3/PI3K signaling crosstalk in iMyc E mu B lymphoma.Mol Cancer. 2010;9:97.
69. Lee YK,Park SY,Kim YM,Lee WS,Park OJ.AMP kinase/cyclooxygenase-2 pathway regulates proliferation and apoptosis of cancer cells treated with quercetin.Exp Mol Med. 2009;41:201-7.
70. Allison SJ,Milner J.SIRT3 is pro-apoptotic and participates in distinct basal apoptotic pathways.Cell Cycle. 2007;6:2669-77.
71. Pfister JA,Ma C,Morrison BE,D'Mello SR.Opposing effects of sirtuins on neuronal survival: SIRT1-mediated neuroprotection is independent of its deacetylase activity.PLoS One. 2008;3:e4090.
72. Marfe G,Tafani M,Indelicato M,et al.Kaempferol induces apoptosis in two different cell lines via Akt inactivation, Bax and SIRT3 activation, and mitochondrial dysfunction.J Cell Biochem. 2009;106:643-50.
73. Grubisha O,Rafty LA,Takanishi CL,et al.Metabolite of SIR2 reaction modulates TRPM2 ion channel.J Biol Chem. 2006;281:14057-65.
74. Zhang YY,Zhou LM.Sirt3 inhibits hepatocellular carcinoma cell growth through reducing Mdm2-mediated p53 degradation.Biochem Biophys Res Commun. 2012;423:26-31.
75. Levine AJ,Momand J,Finlay CA.The p53 tumour suppressor gene.Nature. 1991;351:453-6.
76. Caamano J,Zhang SY,Rosvold EA,Bauer B,Klein-Szanto AJ.p53 alterations in human squamous cell carcinomas and carcinoma cell lines.Am J Pathol. 1993;142:1131-9.
77. Van Damme M,Crompot E,Meuleman N,et al.HDAC isoenzyme expression is deregulated in chronic lymphocytic leukemia B-cells and has a complex prognostic significance.Epigenetics. 2012;7:1403-12.
78. Finley LW,Haigis MC.Metabolic regulation by SIRT3: implications for tumorigenesis.Trends Mol Med. 2012;18:516-23.
79. Haigis MC,Deng CX,Finley LW,Kim HS,Gius D.SIRT3 is a mitochondrial tumor suppressor: a scientific tale that connects aberrant cellular ROS, the Warburg effect, and carcinogenesis.Cancer Res. 2012;72:2468-72.
80. Liu J,Huang J,Yao WY,et al.The origins of vacularization in tumors.Front Biosci. 2012;17:2559-65.
81. Potente M,Ghaeni L,Baldessari D.,et al.SIRT1 controls endothelial angiogenic functions during vascular growth.Genes Dev. 2007;21:2644-58.
82. Fukuda S,Kaga S,Zhan L,et al.Resveratrol ameliorates myocardial damage by inducing vascular endothelial growth factor-angiogenesis and tyrosine kinase receptor Flk-1.Cell Biochem Biophys. 2006;44:43-9.
83. Chen R,Dioum EM,Hogg RT,Gerard RD,Garcia JA.Hypoxia increases sirtuin 1 expression in a hypoxia-inducible factor-dependent manner.J Biol Chem. 2011;286:13869-78.
84. Alcendor RR,Kirshenbaum LA,Imai S,Vatner SF,Sadoshima J.Silent information regulator 2alpha, a longevity factor and class III histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes.Circ Res. 2004;95:971-80.
85. Sano M,Minamino T,Toko H,et al.p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload.Nature. 2007;446:444-8.
86. Qian BZ,Pollard JW.Macrophage diversity enhances tumor progression and metastasis.Cell. 2010;141:39-51.
87. DeNardo DG,Andreu P,Coussens LM.Interactions between lymphocytes and myeloid cells regulate pro- versus anti-tumor immunity.Cancer Metastasis Rev. 2010;29:309-16.
88. Galli M,Van Gool F,Leo O.Sirtuins and inflammation: friends or foes?.Biochem Pharmacol. 2011;81:569-76.
89. Horio Y,Hayashi T,Kuno A,Kunimoto R.Cellular and molecular effects of sirtuins in health and disease.Clin Sci (Lond). 2011;121:191-203.
90. Yeung F,Hoberg JE,Ramsey CS,et al.Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase.EMBO J. 2004;23:2369-80.
91. Kawahara TL,Michishita E,Adler AS,et al.SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span.Cell. 2009;136:62-74.
92. Vakhrusheva O,Smolka C,Gajawada P,et al.Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice.Circ Res. 2008;102:703-10.
93. Van Gool F,Galli M,Gueydan C,et al.Intracellular NAD levels regulate tumor necrosis factor protein synthesis in a sirtuin-dependent manner.Nat Med. 2009;15:206-10.
94. Kamp DW,Shacter E,Weitzman SA.Chronic inflammation and cancer: the role of the mitochondria.Oncology (Williston Park). 2011;25:400 13-10.
95. Koyama T,Kume S,Koya D,et al.SIRT3 attenuates palmitate-induced ROS production and inflammation in proximal tubular cells.Free Radic Biol Med. 2011;51:1258-67.
96. Capettini LS,Montecucco F,Mach F,et al.Role of renin-angiotensin system in inflammation, immunity and aging.Curr Pharm Des. 2012;18:963-70.
97. Ferrer MD,Tauler P,Sureda A,Tur JA,Pons A.Antioxidant regulatory mechanisms in neutrophils and lymphocytes after intense exercise.J Sports Sci. 2009;27:49-58.
98. Mestre-Alfaro A,Ferrer MD,Banquells M,et al.Body temperature modulates the antioxidant and acute immune responses to exercise.Free Radic Res. 2012;46:799-808.
99. Cha EJ,Noh SJ,Kwon KS,et al.Expression of DBC1 and SIRT1 is associated with poor prognosis of gastric carcinoma.Clin Cancer Res. 2009;15:4453-9.
100. Nakane K,Fujita Y,Terazawa R,et al.Inhibition of cortactin and SIRT1 expression attenuates migration and invasion of prostate cancer DU145 cells.Int J Urol. 2012;19:71-9.
101. Frisch SM,Francis H.Disruption of epithelial cell-matrix interactions induces apoptosis.J Cell Biol. 1994;124:619-26.
102. Kamarajan P,Bunek J,Lin Y,Nunez G,Kapila YL.Receptor-interacting protein shuttles between cell death and survival signaling pathways.Mol Biol Cell. 2010;21:481-8.
103. Kurenova E,Xu LH,Yang X,et al.Focal adhesion kinase suppresses apoptosis by binding to the death domain of receptor-interacting protein.Mol Cell Biol. 2004;24:4361-71.
104. Meylan E,Tschopp J.The RIP kinases: crucial integrators of cellular stress.Trends Biochem Sci. 2005;30:151-9.
105. Grimshaw MJ,Cooper L,Papazisis K,et al.Mammosphere culture of metastatic breast cancer cells enriches for tumorigenic breast cancer cells.Breast Cancer Res. 2008;10:R52.
106. Sakuma Y,Takeuchi T,Nakamura Y,et al.Lung adenocarcinoma cells floating in lymphatic vessels resist anoikis by expressing phosphorylated Src.J Pathol. 2010;220:574-85.
107. Iwanicki MP,Davidowitz RA,Ng MR,et al.Ovarian cancer spheroids use myosin-generated force to clear the mesothelium.Cancer Discov. 2011;1:144-57.
108. Temkin V,Huang Q,Liu H,Osada H,Pope RM.Inhibition of ADP/ATP exchange in receptor-interacting protein-mediated necrosis.Mol Cell Biol. 2006;26:2215-25.
109. Kasof GM,Prosser JC,Liu D,Lorenzi MV,Gomes BC.The RIP-like kinase, RIP3, induces apoptosis and NF-kappaB nuclear translocation and localizes to mitochondria.FEBS Lett. 2000;473:285-91.
110. Shen HM,Lin Y,Choksi S,et al.Essential roles of receptor-interacting protein and TRAF2 in oxidative stress-induced cell death.Mol Cell Biol. 2004;24:5914-22.
111. Lin Y,Choksi S,Shen HM,et al.Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation.J Biol Chem. 2004;279:10822-8.
112. Bosch-Presegue L,Vaquero A.The dual role of sirtuins in cancer.Genes Cancer. 2011;2:648-62.
113. Lim CS.SIRT1: tumor promoter or tumor suppressor?.Med Hypotheses. 2006;67:341-4.
114. Deng CX.SIRT1, is it a tumor promoter or tumor suppressor?.Int J Biol Sci. 2009;5:147-52.
115. Galli U,Mesenzani O,Coppo C,et al.Identification of a sirtuin 3 inhibitor that displays selectivity over sirtuin 1 and 2.Eur J Med Chem. 2012;55:58-66.
116. Ota H,Tokunaga E,Chang K,et al.Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells.Oncogene. 2006;25:176-85.
117. Luo J,Nikolaev AY,Imai S,et al.Negative control of p53 by Sir2alpha promotes cell survival under stress.Cell. 2001;107:137-48.
118. Heltweg B,Gatbonton T,Schuler AD,et al.Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes.Cancer Res. 2006;66:4368-77.
119. Villalba JM,Alcain FJ.Sirtuin activators and inhibitors.Biofactors. 2012;38:349-59.
120. Carafa V,Nebbioso A,Altucci L.Sirtuins and disease: the road ahead.Front Pharmacol. 2012;3:4.
121. Camins A,Sureda FX,Junyent F,et al.Sirtuin activators: designing molecules to extend life span.Biochim Biophys Acta. 2010;1799:740-9.
122. Patel KR,Scott E,Brown VA,et al.Clinical trials of resveratrol.Ann N Y Acad Sci. 2011;1215:161-9.