title: Metabolic regulation of Sirtuins upon fasting and the implication for cancer.
abstract: OBJECTIVE
  The purpose of this review is to highlight recent studies on mammalian sirtuins that coordinately regulate cellular metabolic homeostasis upon fasting and to summarize the beneficial effects of fasting on carcinogenesis and cancer therapy.
  
  
  RESULTS
  Recent studies have demonstrated that fasting may protect normal cells and mice from the metabolic conditions that are harmful as well as decrease the incidence of carcinogenesis. Fasting could also slow the tumor growth and augment the efficacy of certain systemic agents/chemotherapy drugs in various cancers. The mechanism behind this proposed idea may be due to, at least in some part, the metabolic regulation by Sirtuin family proteins whose functions are involved in specific aspects of longevity, stress response and metabolism. Sirtuins, particularly SIRT1 and SIRT3, can be activated by fasting and further exhibit their effects in insulin response, antioxidant defense, and glycolysis. Therefore, sirtuins may have anticancer effects by shifting metabolism to a less proliferative cell phenotype as well as less prone to oxidative stress attack.
  
  
  CONCLUSIONS
  The in-depth understanding of the essential role of sirtuins in fasting process may have significant implications in developing a new metabolic diagram of cancer prevention or treatment.
authors.affiliation: Department of Radiation Oncology, Robert Lurie Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA *The first two authors contributed equally to this manuscript.
authors.forename: Yueming
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yufan
authors.initials: Y
authors.lastname: Yan
authors.forename: David R
authors.initials: DR
authors.lastname: Gius
authors.forename: Athanassios
authors.initials: A
authors.lastname: Vassilopoulos
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D004734:Energy Metabolism; D005215:Fasting / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000378:metabolism* / Q000517:prevention & control / Q000628:therapy; D018384:Oxidative Stress; D020239:Receptor Cross-Talk; D056564:Sirtuin 1 / Q000378:metabolism*; D056566:Sirtuin 3 / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism
chemical_list: D000975:Antioxidants; D007328:Insulin; C447939:SIRT1 protein, human; C466093:SIRT3 protein, human; D056564:Sirtuin 1; D056566:Sirtuin 3; D037761:Sirtuins; D005947:Glucose
references.citation: PLoS One. 2011;6(8):e23295
references.pmid: 21858060
references.citation: Science. 2005 Dec 9;310(5754):1641
references.pmid: 16339438
references.citation: Mol Cell Biol. 1990 Aug;10(8):4243-55
references.pmid: 2115122
references.citation: Science. 2009 Jul 10;325(5937):201-4
references.pmid: 19590001
references.citation: Oncogene. 2007 Aug 13;26(37):5489-504
references.pmid: 17694089
references.citation: Science. 2010 Aug 27;329(5995):1012-3; author reply 1013-4
references.pmid: 20798296
references.citation: Genes Dev. 2003 Feb 1;17(3):313-21
references.pmid: 12569120
references.citation: Cancer Res. 1999 Jun 1;59(11):2577-80
references.pmid: 10363976
references.citation: Aging (Albany NY). 2011 Feb;3(2):102-7
references.pmid: 21386137
references.citation: J Altern Complement Med. 2005 Aug;11(4):601-7
references.pmid: 16131283
references.citation: Nature. 2009 Feb 5;457(7230):726-30
references.pmid: 19079239
references.citation: Int J Mol Sci. 2011;12(9):6226-39
references.pmid: 22016654
references.citation: Trends Biochem Sci. 2010 Dec;35(12):669-75
references.pmid: 20863707
references.citation: Int J Biol Sci. 2011;7(5):575-87
references.pmid: 21614150
references.citation: Transl Cancer Res. 2012 Jun 1;1(1):15-21
references.pmid: 22943040
references.citation: J Gerontol A Biol Sci Med Sci. 2006 Sep;61(9):943-50
references.pmid: 16960025
references.citation: Mol Aspects Med. 2010 Apr;31(2):145-70
references.pmid: 20206201
references.citation: Genes Dev. 2009 Dec 15;23(24):2812-7
references.pmid: 20008932
references.citation: Biochim Biophys Acta. 2010 Aug;1804(8):1576-83
references.pmid: 19782772
references.citation: PLoS One. 2009;4(5):e5422
references.pmid: 19412543
references.citation: Metab Brain Dis. 1990 Jun;5(2):65-75
references.pmid: 2385215
references.citation: Aging (Albany NY). 2011 Jun;3(6):635-42
references.pmid: 21701047
references.citation: Cancer Res. 2012 May 15;72(10):2468-72
references.pmid: 22589271
references.citation: Nature. 2000 Nov 9;408(6809):239-47
references.pmid: 11089981
references.citation: Methods Enzymol. 2009;457:137-47
references.pmid: 19426866
references.citation: J Clin Invest. 2011 Nov;121(11):4281-8
references.pmid: 21985785
references.citation: Antonie Van Leeuwenhoek. 2002 Aug;81(1-4):3-13
references.pmid: 12448700
references.citation: Nature. 2009 Jul 30;460(7255):587-91
references.pmid: 19641587
references.citation: Dev Cell. 2005 Nov;9(5):605-15
references.pmid: 16256736
references.citation: Int J Biochem Cell Biol. 2007;39(1):44-84
references.pmid: 16978905
references.citation: FASEB J. 2006 Jul;20(9):1567-9
references.pmid: 16723385
references.citation: Cancer Metastasis Rev. 2004 Aug-Dec;23(3-4):311-22
references.pmid: 15197331
references.citation: Cancer Cell. 2010 Jan 19;17(1):41-52
references.pmid: 20129246
references.citation: Mol Interv. 2007 Jun;7(3):147-56
references.pmid: 17609521
references.citation: Cell. 2006 Jul 28;126(2):257-68
references.pmid: 16873059
references.citation: J Clin Invest. 2010 Apr;120(4):1043-55
references.pmid: 20335657
references.citation: Cancer Cell. 2011 Mar 8;19(3):416-28
references.pmid: 21397863
references.citation: Cold Spring Harb Symp Quant Biol. 2005;70:363-74
references.pmid: 16869773
references.citation: Mech Ageing Dev. 2005 Sep;126(9):923-8
references.pmid: 15941577
references.citation: Liver Transpl. 2009 Oct;15(10):1183-91
references.pmid: 19790167
references.citation: Genes Dev. 2006 Nov 1;20(21):2913-21
references.pmid: 17079682
references.citation: Age (Dordr). 2008 Sep;30(2-3):147-56
references.pmid: 19424864
references.citation: J Cell Biol. 1997 Jun 30;137(7):1581-8
references.pmid: 9199172
references.citation: Mol Cell. 2011 Jan 21;41(2):139-49
references.pmid: 21255725
references.citation: Am J Clin Nutr. 2007 Jul;86(1):7-13
references.pmid: 17616757
references.citation: Science. 1997 Nov 14;278(5341):1319-22
references.pmid: 9360933
references.citation: J Bacteriol. 1988 Sep;170(9):3910-4
references.pmid: 3045081
references.citation: Cell. 2010 Nov 24;143(5):802-12
references.pmid: 21094524
references.citation: Exp Gerontol. 2004 Sep;39(9):1391-400
references.pmid: 15489062
references.citation: Metab Brain Dis. 1988 Dec;3(4):257-63
references.pmid: 3241603
references.citation: Nature. 2009 Apr 9;458(7239):725-31
references.pmid: 19279572
references.citation: ASN Neuro. 2010 Jul 23;2(3):e00038
references.pmid: 20664705
references.citation: Cancer Cell. 2011 Oct 18;20(4):487-99
references.pmid: 22014574
references.citation: Free Radic Biol Med. 2012 Aug 15;53(4):828-33
references.pmid: 22732184
references.citation: Cell Metab. 2010 Dec 1;12(6):662-7
references.pmid: 21109198
references.citation: Cancer. 1997 Oct 1;80(7):1284-93
references.pmid: 9317181
references.citation: J Natl Cancer Inst. 1997 Oct 15;89(20):1489-97
references.pmid: 9337345
references.citation: Trends Mol Med. 2012 Sep;18(9):516-23
references.pmid: 22749020
references.citation: Prostate. 2010 Jul 1;70(10):1037-43
references.pmid: 20166128
references.citation: Mol Cell. 2006 Aug;23(4):607-18
references.pmid: 16916647
references.citation: Proc Natl Acad Sci U S A. 2008 Jun 17;105(24):8215-20
references.pmid: 18378900
references.citation: Ann N Y Acad Sci. 2006 May;1067:182-90
references.pmid: 16803984
references.citation: Carcinogenesis. 2002 May;23(5):817-22
references.pmid: 12016155
references.citation: Trends Pharmacol Sci. 2010 Feb;31(2):89-98
references.pmid: 20097433
references.citation: Aging Cell. 2007 Dec;6(6):759-67
references.pmid: 17877786
references.citation: Cancer Cell. 2013 Apr 15;23(4):450-63
references.pmid: 23562301
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10224-10229
references.pmid: 16788062
references.citation: PLoS Genet. 2008 Jan;4(1):e13
references.pmid: 18225956
references.citation: Nutr Cancer. 2009;61(2):265-75
references.pmid: 19235043
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: Korean J Anesthesiol. 2010 Mar;58(3):277-82
references.pmid: 20498778
references.citation: Mol Cell. 2011 Oct 21;44(2):177-90
references.pmid: 21856199
references.citation: Science. 1982 Mar 12;215(4538):1415-8
references.pmid: 7063854
references.citation: Nature. 2000 Nov 9;408(6809):248-54
references.pmid: 11089982
references.citation: Genes Dev. 2008 Jul 1;22(13):1753-7
references.pmid: 18550784
references.citation: Cell. 2005 Feb 25;120(4):473-82
references.pmid: 15734680
references.citation: Nature. 2001 Mar 8;410(6825):227-30
references.pmid: 11242085
references.citation: Biochemistry. 2010 Jan 19;49(2):304-11
references.pmid: 20000467
references.citation: Sci Transl Med. 2012 Mar 7;4(124):124ra27
references.pmid: 22323820
references.citation: Science. 1956 Aug 10;124(3215):269-70
references.pmid: 13351639
references.citation: Aging Cell. 2010 Feb;9(1):40-53
references.pmid: 19878145
references.citation: Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19611-6
references.pmid: 22106302
references.citation: Cancer Res. 2003 Apr 15;63(8):1752-5
references.pmid: 12702556
references.citation: BMC Biol. 2006 Feb 03;4:1
references.pmid: 16457721
references.citation: Aging (Albany NY). 2009 Dec 31;1(12):988-1007
references.pmid: 20157582
references.citation: Oncogene. 2011 Jul 28;30(30):3305-16
references.pmid: 21516129
references.citation: Hum Genomics. 2011 Jul;5(5):485-96
references.pmid: 21807603
references.citation: Mol Cell Biol. 2007 Dec;27(24):8807-14
references.pmid: 17923681
references.citation: Cell. 2008 Jan 25;132(2):171-6
references.pmid: 18243090
references.citation: Oncogene. 2011 Feb 3;30(5):505-20
references.pmid: 21057541
references.citation: Mol Cell. 2010 Dec 22;40(6):893-904
references.pmid: 21172655
references.citation: PLoS Biol. 2006 Feb;4(2):e31
references.pmid: 16366736
references.citation: Science. 1956 Feb 24;123(3191):309-14
references.pmid: 13298683