Skip to main content
SpringerLink
Log in

Nutrient restriction in combinatory therapy of tumors

  • Reviews
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

The main objective of anticancer treatment is the elimination of degenerated cells by the induction of programmed cell death. Various chemotherapy drugs and radiation are able to activate cell death mechanisms in tumors. However, unfortunately, monotherapy will always be insufficiently effective because of the variety and virulence of tumors, as well as their ability to develop resistance to drugs. Moreover, monotherapy might constrain many negative side effects. Therefore, the combination of different approaches and/or drugs will increase the efficiency of treatment. One such promising approach is the combination of nutrient restriction (NR) and various chemotherapeutic drugs. This approach may not only affect the autophagy but also influence apoptotic cell death. This review is focused on the potential of NR use in anticancer therapy, as well as the molecular mechanisms underlying this approach.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ATG:

genes associated with autophagy

CRM:

calorie restriction mimetics

ER:

endoplasmic reticulum

IGF-1:

insulin-like growth factor-1

OMMP:

the outer mitochondrial membrane permeabilization

PCD:

programmed cell death

ROS:

reactive oxygen species

SOD2:

superoxide dismutase 2

TNF:

tumor necrosis factor

xIAP:

an inhibitor of apoptotic protein associated with the X-chromosome

PI3P:

phatidylinositol-3-phosphate

AMPK:

AMP-dependent kinase

References

  1. Kerr J.F., Wyllie A.H., Currie A.R. 1972. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer. 26, 239–257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lockshin R.A., Williams C.M. 1964. Programmed cell death—II. Endocrine potentiation of the breakdown of the intersegmental muscles of silkmoths. J. Insect Physiol. 10, 643–649.

    CAS  Google Scholar 

  3. Galluzzi L., Vitale I., Abrams J.M., Alnemri E.S., Baehrecke E.H., Blagosklonny M. V, Dawson T.M., Dawson V.L., El-Deiry W.S., Fulda S., Gottlieb E., Green D.R., Hengartner M.O., Kepp O., Knight R.A., et al. 2012. Molecular definitions of cell death subroutines: Recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ. 19, 107–120.

    Article  CAS  PubMed  Google Scholar 

  4. Galluzzi L., Vitale I., Vacchelli E., Kroemer G. 2011. Cell death signaling and anticancer therapy. Front. Oncol. 1, 5.

    PubMed  PubMed Central  Google Scholar 

  5. Fadok V.A., Bratton D.L., Frasch S.C., Warner M.L., Henson P.M. 1998. The role of phosphatidylserine in recognition of apoptotic cells by phagocytes. Cell Death Differ. 5, 551–562.

    Article  CAS  PubMed  Google Scholar 

  6. Obeid M., Tesniere A., Ghiringhelli F., Fimia G.M., Apetoh L., Perfettini J.-L., Castedo M., Mignot G., Panaretakis T., Casares N., Mé tivier D., Larochette N., van Endert P., Ciccosanti F., Piacentini M., et al. 2007. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat. Med. 13, 54–61.

    Article  CAS  PubMed  Google Scholar 

  7. Martinon F., Tschopp J. 2004. Inflammatory caspases: Linking an intracellular innate immune system to autoinflammatory diseases. Cell. 117, 561–574.

    Article  CAS  PubMed  Google Scholar 

  8. Vakifahmetoglu-Norberg H., Zhivotovsky B. 2010). The unpredictable caspase-2: What can it do? Trends Cell Biol. 20, 150–159.

    Article  CAS  PubMed  Google Scholar 

  9. Tsujimoto Y. 1998). Role of Bcl-2 family proteins in apoptosis: Apoptosomes or mitochondria? Genes Cells. 3, 697–707.

    Article  CAS  PubMed  Google Scholar 

  10. Miyashita T., Reed J.C. 1995. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell. 80, 293–299.

    Article  CAS  PubMed  Google Scholar 

  11. Chipuk J.E., Kuwana T., Bouchier-Hayes L., Droin N.M., Newmeyer D.D., Schuler M., Green D.R. 2004. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science. 303, 1010–1014.

    Article  CAS  PubMed  Google Scholar 

  12. Hemann M.T., Lowe S.W. 2006. The p53-Bcl-2 connection. Cell Death Differ. 13, 1256–1259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Pietsch E.C., Perchiniak E., Canutescu A.A., Wang G., Dunbrack R.L., Murphy M.E. 2008. Oligomerization of BAK by p53 utilizes conserved residues of the p53 DNA binding domain. J. Biol. Chem. 283, 21294–21304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cain K., Bratton S.B., Cohen G.M. 2002. The Apaf-1 apoptosome: A large caspase-activating complex. Biochimie. 84, 203–214.

    Article  CAS  PubMed  Google Scholar 

  15. Lavrik I.N., Krammer P.H. 2012. Regulation of CD95/Fas signaling at the DISC. Cell Death Differ. 19, 36–41.

    Article  CAS  PubMed  Google Scholar 

  16. Dickens L.S., Powley I.R., Hughes M.A., MacFarlane M. 2012. The “complexities” of life and death: Death receptor signalling platforms. Exp. Cell Res. 318, 1269–1277.

    Article  CAS  PubMed  Google Scholar 

  17. Li H., Zhu H., Xu C.J., Yuan J. 1998. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell. 94, 491–501.

    Article  CAS  PubMed  Google Scholar 

  18. Zamaraev A.V., Kopeina G.S., Zhivotovsky B., Lavrik I.N. 2015. Cell death controlling complexes and their potential therapeutic role. Cell. Mol. Life Sci. 72, 505–517.

    Article  CAS  PubMed  Google Scholar 

  19. Eguchi K. 2001. Apoptosis in autoimmune diseases. Intern. Med. 40, 275–284.

    Article  CAS  PubMed  Google Scholar 

  20. Lowe S.W., Lin A.W. 2000. Apoptosis in cancer. Carcinogenesis. 21, 485–495.

    Article  CAS  PubMed  Google Scholar 

  21. Glick D., Barth S., Macleod K.F. 2010. Autophagy: Cellular and molecular mechanisms. J. Pathol. 221, 3–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Nakatogawa H., Suzuki K., Kamada Y., Ohsumi Y. 2009. Dynamics and diversity in autophagy mechanisms: Lessons from yeast. Nat. Rev. Mol. Cell Biol. 10, 458–467.

    Article  CAS  PubMed  Google Scholar 

  23. Kabeya Y., Kamada Y., Baba M., Takikawa H., Sasaki M., Ohsumi Y. 2005. Atg17 functions in cooperation with Atg1 and Atg13 in yeast autophagy. Mol. Biol. Cell. 16, 2544–2553.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kamada Y., Funakoshi T., Shintani T., Nagano K., Ohsumi M., Ohsumi Y. 2000. Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J. Cell Biol. 150, 1507–1513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Burman C., Ktistakis N.T. 2010. Regulation of autophagy by phosphatidylinositol 3-phosphate. FEBS Lett. 584, 1302–1312.

    Article  CAS  PubMed  Google Scholar 

  26. Kihara A., Noda T., Ishihara N., Ohsumi Y. 2001. Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J. Cell Biol. 152, 519–530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kihara A., Kabeya Y., Ohsumi Y., Yoshimori T. 2001. Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network. EMBO Rep. 2, 330–335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sun Q., Fan W., Chen K., Ding X., Chen S., Zhong Q. 2008. Identification of Barkor as a mammalian autophagy- specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase. Proc. Natl. Acad. Sci. U. S. A. 105, 19211–19216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Li X., Yan J., Wang L., Xiao F., Yang Y., Guo X., Wang H. 2013. Beclin1 inhibition promotes autophagy and decreases gemcitabine-induced apoptosis in Miapaca2 pancreatic cancer cells. Cancer Cell Int. 13, 26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ichimura Y., Kirisako T., Takao T., Satomi Y., Shimonishi Y., Ishihara N., Mizushima N., Tanida I., Kominami E., Ohsumi M., Noda T., Ohsumi Y. 2000. A ubiquitin-like system mediates protein lipidation. Nature. 408, 488–492.

    Article  CAS  PubMed  Google Scholar 

  31. Pankiv S., Clausen T.H., Lamark T., Brech A., Bruun J.-A., Outzen H., Ø vervatn A., Bjørkø y G., Johansen T. 2007. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J. Biol. Chem. 282, 24131–24145.

    Article  CAS  PubMed  Google Scholar 

  32. Narendra D., Kane L.A., Hauser D.N., Fearnley I.M., Youle R.J. 2010. p62/SQSTM1 is required for Parkininduced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy. 6, 1090–1106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Mizushima N. 2007. Autophagy: Process and function. Genes Dev. 21, 2861–2873.

    Article  CAS  PubMed  Google Scholar 

  34. Maiuri M.C., Zalckvar E., Kimchi A., Kroemer G. 2007. Self-eating and self-killing: Crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 8, 741–752.

    Article  CAS  PubMed  Google Scholar 

  35. Boya P., Gonzá lez-Polo R.-A., Casares N., Perfettini J.-L., Dessen P., Larochette N., Mé tivier D., Meley D., Souquere S., Yoshimori T., Pierron G., Codogno P., Kroemer G. 2005. Inhibition of macroautophagy triggers apoptosis. Mol. Cell. Biol. 25, 1025–1040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Carew J.S., Medina E.C., Esquivel J.A., Mahalingam D., Swords R., Kelly K., Zhang H., Huang P., Mita A.C., Mita M.M., Giles F.J., Nawrocki S.T. 2010. Autophagy inhibition enhances vorinostat-induced apoptosis via ubiquitinated protein accumulation. J. Cell. Mol. Med. 14, 2448–2459.

    Article  CAS  PubMed  Google Scholar 

  37. Shimizu S., Kanaseki T., Mizushima N., Mizuta T., Arakawa-Kobayashi S., Thompson C.B., Tsujimoto Y. 2004. Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat. Cell Biol. 6, 1221–1228.

    Article  CAS  PubMed  Google Scholar 

  38. Marquez R.T., Xu L. 2012. Bcl-2:Beclin 1 complex: Multiple, mechanisms regulating autophagy/apoptosis toggle switch. Am. J. Cancer Res. 2, 214–221.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Maiuri M.C., Criollo A., Tasdemir E., Vicencio J.M., Tajeddine N., Hickman J.A., Geneste O., Kroemer G. 2014. BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and Bcl-2/Bcl-X L. Autophagy. 3, 374–376.

    Article  Google Scholar 

  40. Sinha S., Levine B. 2008. The autophagy effector Beclin 1: A novel BH3-only protein. Oncogene. 27, Suppl. 1, S137–S148.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mariño G., Niso-Santano M., Baehrecke E.H., Kroemer G. 2014. Self-consumption: The interplay of autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 15, 81–94.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Yousefi S., Perozzo R., Schmid I., Ziemiecki A., Schaffner T., Scapozza L., Brunner T., Simon H.-U. 2006. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat. Cell Biol. 8, 1124–1132.

    Article  CAS  PubMed  Google Scholar 

  43. Wirawan E., Van de Walle L., Kersse K., Cornelis S., Claerhout S., Vanoverberghe I., Roelandt R., de Rycke R., Verspurten J., Declercq W., Agostinis P., Vanden Berghe T., Lippens S., Vandenabeele P. 2010. Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria. Cell Death Dis. 1, e18.

    Article  CAS  Google Scholar 

  44. Beigneux A.P., Kosinski C., Gavino B., Horton J.D., Skarnes W.C., Young S.G. 2004. ATP-citrate lyase deficiency in the mouse. J. Biol. Chem. 279, 9557–9564.

    Article  CAS  PubMed  Google Scholar 

  45. Wellen K.E., Thompson C.B. 2012. A two-way street: Reciprocal regulation of metabolism and signalling. Nat. Rev. Mol. Cell Biol. 13, 270–276.

    CAS  PubMed  Google Scholar 

  46. Mariño G., Pietrocola F., Eisenberg T., Kong Y., Malik S.A., Andryushkova A., Schroeder S., Pendl T., Harger A., Niso-Santano M., Zamzami N., Scoazec M., Durand S., Enot D.P., Fernández Á.F., et al. 2014. Regulation of autophagy by cytosolic acetyl-coenzyme A. Mol. Cell. 53, 710–725.

    Article  PubMed  CAS  Google Scholar 

  47. Lee I.H., Cao L., Mostoslavsky R., Lombard D.B., Liu J., Bruns N.E., Tsokos M., Alt F.W., Finkel T. 2008. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc. Natl. Acad. Sci. U. S. A. 105, 3374–3379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Vassilopoulos A., Fritz K.S., Petersen D.R., Gius D. 2011. The human sirtuin family: Evolutionary divergences and functions. Hum. Genomics. 5, 485–496.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Cohen H.Y., Miller C., Bitterman K.J., Wall N.R., Hekking B., Kessler B., Howitz K.T., Gorospe M., de Cabo R., Sinclair D.A. 2004. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science. 305, 390–392.

    Article  CAS  PubMed  Google Scholar 

  50. Chen D., Steele A.D., Lindquist S., Guarente L. 2005. Increase in activity during calorie restriction requires Sirt1. Science. 310, 1641.

    Article  CAS  PubMed  Google Scholar 

  51. Luo J., Nikolaev A.Y., Imai S., Chen D., Su F., Shiloh A., Guarente L., Gu W. 2001. Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell. 107, 137–148.

    Article  CAS  PubMed  Google Scholar 

  52. Jeong J., Juhn K., Lee H., Kim S.-H., Min B.-H., Lee K.-M., Cho M.-H., Park G.-H., Lee K.-H. 2007. SIRT1 promotes DNA repair activity and deacetylation of Ku70. Exp. Mol. Med. 39, 8–13.

    Article  CAS  PubMed  Google Scholar 

  53. Wang R.-H., Sengupta K., Li C., Kim H.-S., Cao L., Xiao C., Kim S., Xu X., Zheng Y., Chilton B., Jia R., Zheng Z.-M., Appella E., Wang X.W., Ried T., Deng C.-X. 2008. Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell. 14, 312–323.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Giannakou M.E., Partridge L. 2004. The interaction between FOXO and SIRT1: Tipping the balance towards survival. Trends Cell Biol. 14, 408–412.

    Article  CAS  PubMed  Google Scholar 

  55. Shaw R.J. 2009. LKB1 and AMP-activated protein kinase control of mTOR signalling and growth. Acta Physiol. (Oxf.). 196, 65–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kamada Y., Yoshino K., Kondo C., Kawamata T., Oshiro N., Yonezawa K., Ohsumi Y. 2010. Tor directly controls the Atg1 kinase complex to regulate autophagy. Mol. Cell. Biol. 30, 1049–1058.

    Article  CAS  PubMed  Google Scholar 

  57. Kim J., Kundu M., Viollet B., Guan K.-L. 2011. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat. Cell Biol. 13, 132–141.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Meynet O., Zunino B., Happo L., Pradelli L.A., Chiche J., Jacquin M.A., Mondragó n L., Tanti J.-F., Taillan B., Garnier G., Reverso-Meinietti J., Mounier N., Michiels J.-F., Michalak E.M., Carles M., et al. 2013. Caloric restriction modulates Mcl-1 expression and sensitizes lymphomas to BH3 mimetic in mice. Blood. 122, 2402–2411.

    Article  CAS  PubMed  Google Scholar 

  59. Pelicano H., Martin D.S., Xu R.-H., Huang P. 2006. Glycolysis inhibition for anticancer treatment. Oncogene. 25, 4633–4646.

    Article  CAS  PubMed  Google Scholar 

  60. Zachar Z., Marecek J., Maturo C., Gupta S., Stuart S.D., Howell K., Schauble A., Lem J., Piramzadian A., Karnik S., Lee K., Rodriguez R., Shorr R., Bingham P.M. 2011. Non-redox-active lipoate derivates disrupt cancer cell mitochondrial metabolism and are potent anticancer agents in vivo. J. Mol. Med. 89, 1137–1148.

    Article  CAS  PubMed  Google Scholar 

  61. Ren X.-R., Wang J., Osada T., Mook R.A., Morse M.A., Barak L.S., Lyerly H.K., Chen W. 2015. Perhexiline promotes HER3 ablation through receptor internalization and inhibits tumor growth. Breast Cancer Res. 17, 20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Samudio I., Harmancey R., Fiegl M., Kantarjian H., Konopleva M., Korchin B., Kaluarachchi K., Bornmann W., Duvvuri S., Taegtmeyer H., Andreeff M. 2010. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J. Clin. Invest. 120, 142–156.

    Article  CAS  PubMed  Google Scholar 

  63. Andela V.B., Altuwaijri S., Wood J., Rosier R.N. 2005. Inhibition of beta-oxidative respiration is a therapeutic window associated with the cancer chemo-preventive activity of PPARgamma agonists. FEBS Lett. 579, 1765–1769.

    Article  CAS  PubMed  Google Scholar 

  64. Hanai J.-I., Doro N., Seth P., Sukhatme V.P. 2013. ATP citrate lyase knockdown impacts cancer stem cells in vitro. Cell Death Dis. 4, e696.

    Article  CAS  Google Scholar 

  65. Hatzivassiliou G., Zhao F., Bauer D.E., Andreadis C., Shaw A.N., Dhanak D., Hingorani S.R., Tuveson D.A., Thompson C.B. 2005. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell. 8, 311–321.

    Article  CAS  PubMed  Google Scholar 

  66. Kang S.-K., Cha S.-H., Jeon H.-G. 2006. Curcumininduced histone hypoacetylation enhances caspase-3- dependent glioma cell death and neurogenesis of neural progenitor cells. Stem Cell Dev. 15, 165–174.

    Article  CAS  Google Scholar 

  67. Shakibaei M., Mobasheri A., Lueders C., Busch F., Shayan P., Goel A. 2013. Curcumin enhances the effect of chemotherapy against colorectal cancer cells by inhibition of NF-?B and Src protein kinase signaling pathways. PLoS ONE. 8, e57218.

    Article  CAS  Google Scholar 

  68. Wu Y., He L., Zhang L., Chen J., Yi Z., Zhang J., LiuM., Pang X. 2011. Anacardic acid (6-pentadecylsalicylic acid) inhibits tumor angiogenesis by targeting Src/FAK/Rho GTPases signaling pathway. J. Pharmacol. Exp. Ther. 339, 403–411.

    Article  CAS  PubMed  Google Scholar 

  69. Lashinger L.M., Malone L.M., Brown G.W., Daniels E.A., Goldberg J.A., Otto G., Fischer S.M., Hursting S.D. 2011. Rapamycin partially mimics the anticancer effects of calorie restriction in a murine model of pancreatic cancer. Cancer Prev. Res. 4, 1041–1051.

    Article  CAS  Google Scholar 

  70. de Angel R.E., Conti C.J., Wheatley K.E., Brenner A.J., Otto G., Degraffenried L.A., Hursting S.D. 2013. The enhancing effects of obesity on mammary tumor growth and Akt/mTOR pathway activation persist after weight loss and are reversed by RAD001. Mol. Carcinog. 52, 446–458.

    Article  PubMed  CAS  Google Scholar 

  71. Fouad M.A., Agha A.M., Merzabani M.M. Al, Shouman S.A. 2013. Resveratrol inhibits proliferation, angiogenesis and induces apoptosis in colon cancer cells: Calorie restriction is the force to the cytotoxicity. Hum. Exp. Toxicol. 32, 1067–1080.

    Article  CAS  PubMed  Google Scholar 

  72. Angst E., Park J.L., Moro A., Lu Q.-Y., Lu X., Li G., King J., Chen M., Reber H.A., Go V.L.W., Eibl G., Hines O.J. 2013. The flavonoid quercetin inhibits pancreatic cancer growth in vitro and in vivo. Pancreas. 42, 223–229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Pollak M.N. 2012. Investigating metformin for cancer prevention and treatment: The end of the beginning. Cancer Discov. 2, 778–790.

    Article  CAS  PubMed  Google Scholar 

  74. Orecchioni S., Reggiani F., Talarico G., Mancuso P., Calleri A., Gregato G., Labanca V., Noonan D.M., Dallaglio K., Albini A., Bertolini F. 2015. The biguanides metformin and phenformin inhibit angiogenesis, local and metastatic growth of breast cancer by targeting both neoplastic and microenvironment cells. Int. J. Cancer. 136, e534–E544.

    Article  CAS  Google Scholar 

  75. Zadra G., Photopoulos C., Tyekucheva S., Heidari P., Weng Q.P., Fedele G., Liu H., Scaglia N., Priolo C., Sicinska E., Mahmood U., Signoretti S., Birnberg N., Loda M. 2014. A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis. EMBO Mol. Med. 6, 519–538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Orrenius S., Gogvadze V., Zhivotovsky B. 2007. Mitochondrial oxidative stress: Implications for cell death. Annu. Rev. Pharmacol. Toxicol. 47, 143–183.

    Article  CAS  PubMed  Google Scholar 

  77. Li L., Chen Y., Gibson S.B. 2013. Starvation-induced autophagy is regulated by mitochondrial reactive oxygen species leading to AMPK activation. Cell. Signal. 25, 50–65.

    Article  CAS  PubMed  Google Scholar 

  78. Yang W., Hong Y.H., Shen X.Q., Frankowski C., Camp H.S., Leff T. 2001. Regulation of transcription by AMP-activated protein kinase: Phosphorylation of p300 blocks its interaction with nuclear receptors. J. Biol. Chem. 276, 38341–38344.

    Article  CAS  PubMed  Google Scholar 

  79. Ruderman N.B., Xu X.J., Nelson L., Cacicedo J.M., Saha A.K., Lan F., Ido Y. 2010. AMPK and SIRT1: A long-standing partnership? Am. J. Physiol. Endocrinol. Metab. 298, e751–E760.

    Article  CAS  Google Scholar 

  80. Guarente L. 2005. Calorie restriction and SIR2 genes: Towards a mechanism. Mech. Ageing Dev. 126, 923–928.

    Article  CAS  PubMed  Google Scholar 

  81. Houthoofd K., Vanfleteren J.R. 2006. The longevity effect of dietary restriction in Caenorhabditis elegans. Exp. Gerontol. 41, 1026–1031.

    Article  CAS  PubMed  Google Scholar 

  82. Weindruch R. The retardation of aging by caloric restriction: Studies in rodents and primates. Toxicol. Pathol. 24, 742–745.

  83. Colman R.J., Anderson R.M., Johnson S.C., Kastman E.K., Kosmatka K.J., Beasley T.M., Allison D.B., Cruzen C., Simmons H.A., Kemnitz J.W., Weindruch R. 2009. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 325, 201–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Colman R.J., Beasley T.M., Kemnitz J.W., Johnson S.C., Weindruch R., Anderson R.M. 2014. Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat. Commun. 5, 3557.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Mattison J.A., Roth G.S., Beasley T.M., Tilmont E.M., Handy A.M., Herbert R.L., Longo D.L., Allison D.B., Young J.E., Bryant M., Barnard D., Ward W.F., Qi W., Ingram D.K., de Cabo R. 2012. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. 489, 318–321.

    Article  CAS  PubMed  Google Scholar 

  86. Kaeberlein M., McVey M., Guarente L. 1999. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 13, 2570–2580.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Rogina B., Helfand S.L. 2004. Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc. Natl. Acad. Sci. U. S. A. 101, 15998–16003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Tissenbaum H.A., Guarente L. 2001. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature. 410, 227–230.

    Article  CAS  PubMed  Google Scholar 

  89. Bordone L., Cohen D., Robinson A., Motta M.C., vanVeen E., Czopik A., Steele A.D., Crowe H., Marmor S., Luo J., Gu W., Guarente L. 2007. SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell. 6, 759–767.

    Article  CAS  PubMed  Google Scholar 

  90. Boily G., Seifert E.L., Bevilacqua L., He X.H., Sabourin G., Estey C., Moffat C., Crawford S., Saliba S., Jardine K., Xuan J., Evans M., Harper M.-E., McBurney M.W. 2008. SirT1 regulates energy metabolism and response to caloric restriction in mice. PLoS ONE. 3, e1759.

    Article  CAS  Google Scholar 

  91. Yamamoto M., Clark J.D., Pastor J. V., Gurnani P., Nandi A., Kurosu H., Miyoshi M., Ogawa Y., Castrillon D.H., Rosenblatt K.P., Kuro-o M. 2005. Regulation of oxidative stress by the anti-aging hormone Klotho. J. Biol. Chem. 280, 38029–38034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Qiu X., Brown K., Hirschey M.D., Verdin E., Chen D. 2010. Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab. 12, 662–667.

    Article  CAS  PubMed  Google Scholar 

  93. Sohal R.S., Weindruch R. 1996. Oxidative stress, caloric restriction, and aging. Science. 273, 59–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Calle E.E., Kaaks R. 2004. Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms. Nat. Rev. Cancer. 4, 579–591.

    Article  CAS  PubMed  Google Scholar 

  95. Mukherjee P., Sotnikov A. V, Mangian H.J., Zhou J.R., Visek W.J., Clinton S.K. 1999. Energy intake and prostate tumor growth, angiogenesis, and vascular endothelial growth factor expression. J. Natl. Cancer Inst. 91, 512–523.

    Article  CAS  PubMed  Google Scholar 

  96. Mulrooney T.J., Marsh J., Urits I., Seyfried T.N., Mukherjee P. 2011. Influence of caloric restriction on constitutive expression of NF-?B in an experimental mouse astrocytoma. PLoS ONE. 6, e18085.

    Article  CAS  Google Scholar 

  97. de Lorenzo M.S., Baljinnyam E., Vatner D.E., Abarzú a P., Vatner S.F., Rabson A.B. 2011. Caloric restriction reduces growth of mammary tumors and metastases. Carcinogenesis. 32, 1381–1387.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Lv M., Zhu X., Wang H., Wang F., Guan W. 2014. Roles of caloric restriction, ketogenic diet and intermittent fasting during initiation, progression and metastasis of cancer in animal models: A systematic review and meta-analysis. PLoS ONE. 9, e115147.

    Article  CAS  Google Scholar 

  99. Michels K.B., Ekbom A. 2004. Caloric restriction and incidence of breast cancer. J. Am. Med. Assoc. 291, 1226–1230.

    Article  CAS  Google Scholar 

  100. Hursting S.D., Switzer B.R., French J.E., Kari F.W. 1993. The growth hormone: Insulin-like growth factor 1 axis is a mediator of diet restriction-induced inhibition of mononuclear cell leukemia in Fischer rats. Cancer Res. 53, 2750–2757.

    CAS  PubMed  Google Scholar 

  101. Gao Y., Katki H., Graubard B., Pollak M., Martin M., Tao Y., Schoen R.E., Church T., Hayes R.B., Greene M.H., Berndt S.I. 2012. Serum IGF1, IGF2 and IGFBP3 and risk of advanced colorectal adenoma. Int. J. Cancer. 131, e105–E113.

    Article  CAS  Google Scholar 

  102. Renehan A.G., Zwahlen M., Minder C., O’ Dwyer S.T., Shalet S.M., Egger M. 2004. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: Systematic review and meta-regression analysis. Lancet (London). 363, 1346–1353.

    Article  CAS  Google Scholar 

  103. Price A.J., Allen N.E., Appleby P.N., Crowe F.L., Travis R.C., Tipper S.J., Overvad K., Grønbæ k H., Tjø nneland A., Johnsen N.F., Rinaldi S., Kaaks R., Lukanova A., Boeing H., Aleksandrova K., et al. 2012. Insulin-like growth factor-I concentration and risk of prostate cancer: Results from the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol. Biomarkers Prev. 21, 1531–1541.

    Article  CAS  PubMed  Google Scholar 

  104. Dunn S.E., Kari F.W., French J., Leininger J.R., Travlos G., Wilson R., Barrett J.C. 1997. Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-deficient mice. Cancer Res. 57, 4667–4672.

    CAS  PubMed  Google Scholar 

  105. Ikeno Y., Hubbard G.B., Lee S., Cortez L.A., Lew C.M., Webb C.R., Berryman D.E., List E.O., Kopchick J.J., Bartke A. 2009. Reduced incidence and delayed occurrence of fatal neoplastic diseases in growth hormone receptor/binding protein knockout mice. J. Gerontol. A. Biol. Sci. Med. Sci. 64, 522–529.

    Article  PubMed  CAS  Google Scholar 

  106. Bartke A., Chandrashekar V., Bailey B., Zaczek D., Turyn D. Consequences of growth hormone (GH) overexpression and GH resistance. Neuropeptides. 36, 201–208.

  107. Lee C., Safdie F.M., Raffaghello L., Wei M., Madia F., Parrella E., Hwang D., Cohen P., Bianchi G., Longo V.D. 2010. Reduced levels of IGF-I mediate differential protection of normal and cancer cells in response to fasting and improve chemotherapeutic index. Cancer Res. 70, 1564–1572.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Levine M.E., Suarez J.A., Brandhorst S., Balasubramanian P., Cheng C.-W., Madia F., Fontana L., Mirisola M.G., Guevara-Aguirre J., Wan J., Passarino G., Kennedy B.K., Wei M., Cohen P., Crimmins E.M., Longo V.D. 2014. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 19, 407–417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Fresno Vara J.A., Casado E., de Castro J., Cejas P., Belda-Iniesta C., González-Barón M. 2004. PI3K/Akt signalling pathway and cancer. Cancer Treat. Rev. 30, 193–204.

    Article  PubMed  CAS  Google Scholar 

  110. Bos J.L. 1989. RAS oncogenes in human cancer: A review. Cancer Res. 49, 4682–4689.

    CAS  PubMed  Google Scholar 

  111. Downward J. 2003. Targeting RAS signalling pathways in cancer therapy. Nat. Rev. Cancer. 3, 11–22.

    Article  CAS  PubMed  Google Scholar 

  112. Hahn-Windgassen A., Nogueira V., Chen C.-C., Skeen J.E., Sonenberg N., Hay N. 2005. Akt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity. J. Biol. Chem. 280, 32081–32089.

    Article  CAS  PubMed  Google Scholar 

  113. Altomare D.A., Testa J.R. 2005. Perturbations of the AKT signaling pathway in human cancer. Oncogene. 24, 7455–7464.

    Article  CAS  PubMed  Google Scholar 

  114. Herrero-Martín G., Høyer-Hansen M., García-García C., Fumarola C., Farkas T., López-Rivas A., Jäättelä M. 2009. TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells. EMBO J. 28, 677–685.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Park H.U., Suy S., Danner M., Dailey V., Zhang Y., Li H., Hyduke D.R., Collins B.T., Gagnon G., Kallakury B., Kumar D., Brown M.L., Fornace A., Dritschilo A., Collins S.P. 2009. AMP-activated protein kinase promotes human prostate cancer cell growth and survival. Mol. Cancer Ther. 8, 733–741.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Mukherjee P., Mulrooney T.J., Marsh J., Blair D., Chiles T.C., Seyfried T.N. 2008. Differential effects of energy stress on AMPK phosphorylation and apoptosis in experimental brain tumor and normal brain. Mol. Cancer. 7, 37.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Faubert B., Boily G., Izreig S., Griss T., Samborska B., Dong Z., Dupuy F., Chambers C., Fuerth B.J., Viollet B., Mamer O.A., Avizonis D., DeBerardinis R.J., Siegel P.M., Jones R.G. 2013. AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo. Cell Metab. 17, 113–124.

    Article  CAS  PubMed  Google Scholar 

  118. Vigneri P.G., Tirrò E., Pennisi M.S., Massimino M., Stella S., Romano C., Manzella L. 2015. The insulin/ IGF system in colorectal cancer development and resistance to therapy. Front. Oncol. 5, 230.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Majeed N., Blouin M.-J., Kaplan-Lefko P.J., Barry-Shaw J., Greenberg N.M., Gaudreau P., Bismar T.A., Pollak M. 2005. A germ line mutation that delays prostate cancer progression and prolongs survival in a murine prostate cancer model. Oncogene. 24, 4736–4740.

    Article  CAS  PubMed  Google Scholar 

  120. Sekharam M., Zhao H., Sun M., Fang Q., Zhang Q., Yuan Z., Dan H.C., Boulware D., Cheng J.Q., Coppola D. 2003. Insulin-like growth factor 1 receptor enhances invasion and induces resistance to apoptosis of colon cancer cells through the Akt/Bcl-x(L) pathway. Cancer Res. 63, 7708–7716.

    CAS  PubMed  Google Scholar 

  121. Warburg O. 1956. On the origin of cancer cells. Science. 123, 309–314.

    Article  CAS  PubMed  Google Scholar 

  122. Van der Heiden M.G., Cantley L.C., Thompson C.B. 2009. Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science. 324, 1029–1033.

    Article  CAS  Google Scholar 

  123. Gatenby R.A., Gillies R.J. 2004. Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer. 4, 891–899.

    Article  CAS  PubMed  Google Scholar 

  124. Elstrom R.L., Bauer D.E., Buzzai M., Karnauskas R., Harris M.H., Plas D.R., Zhuang H., Cinalli R.M., Alavi A., Rudin C.M., Thompson C.B. 2004. Akt stimulates aerobic glycolysis in cancer cells. Cancer Res. 64, 3892–3899.

    Article  CAS  PubMed  Google Scholar 

  125. DeBerardinis R.J., Lum J.J., Hatzivassiliou G., Thompson C.B. 2008. The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 7, 11–20.

    Article  CAS  PubMed  Google Scholar 

  126. Cardaci S., Ciriolo M.R. 2012. TCA cycle defects and cancer: When metabolism tunes redox state. Int. J. Cell Biol. 2012, 161837. doi 10.1155/2012/161837

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Xie J., Wu H., Dai C., Pan Q., Ding Z., Hu D., Ji B., Luo Y., Hu X. 2014. Beyond Warburg effect: Dual metabolic nature of cancer cells. Sci. Rep. 4, 4927.

    PubMed  PubMed Central  Google Scholar 

  128. Jackson J.R., Seed M.P., Kircher C.H., Willoughby D.A., Winkler J.D. 1997. The codependence of angiogenesis and chronic inflammation. FASEB J. 11, 457–465.

    CAS  PubMed  Google Scholar 

  129. Kobayashi H., Lin P.C. 2009. Angiogenesis links chronic inflammation with cancer. Meth. Mol. Biol. 511, 185–191.

    Article  CAS  Google Scholar 

  130. Mukherjee P., El-Abbadi M.M., Kasperzyk J.L., Ranes M.K., Seyfried T.N. 2002. Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model. Br. J. Cancer. 86, 1615–1621.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Anzo M., Cobb L.J., Hwang D.L., Mehta H., Said J.W., Yakar S., LeRoith D., Cohen P. 2008. Targeted deletion of hepatic Igf1 in TRAMP mice leads to dramatic alterations in the circulating insulin-like growth factor axis but does not reduce tumor progression. Cancer Res. 68, 3342–3349.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Raffaghello L., Lee C., Safdie F.M., Wei M., Madia F., Bianchi G., Longo V.D. 2008. Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proc. Natl. Acad. Sci. U. S. A. 105, 8215–8220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Shi Y., Felley-Bosco E., Marti T.M., Orlowski K., Pruschy M., Stahel R.A. 2012. Starvation-induced activation of ATM/Chk2/p53 signaling sensitizes cancer cells to cisplatin. BMC Cancer. 12, 571.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Bianchi G., Martella R., Ravera S., Marini C., Capitanio S., Orengo A., Emionite L., Lavarello C., Amaro A., Petretto A., Pfeffer U., Sambuceti G., Pistoia V., Raffaghello L., Longo V.D. 2015. Fasting induces anti- Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models. Oncotarget. 6, 11806–11819.

    Article  PubMed  PubMed Central  Google Scholar 

  135. Krause D.S., van Etten R.A. 2005. Tyrosine kinases as targets for cancer therapy. N. Engl. J. Med. 353, 172–187.

    Article  CAS  PubMed  Google Scholar 

  136. Caffa I., D’ Agostino V., Damonte P., Soncini D., Cea M., Monacelli F., Odetti P., Ballestrero A., Provenzani A., Longo V.D., Nencioni A. 2015. Fasting potentiates the anticancer activity of tyrosine kinase inhibitors by strengthening MAPK signaling inhibition. Oncotarget. 6, 11820–11832.

    Article  PubMed  PubMed Central  Google Scholar 

  137. Saleh A.D., Simone B.A., Palazzo J., Savage J.E., Sano Y., Dan T., Jin L., Champ C.E., Zhao S., Lim M., Sotgia F., Camphausen K., Pestell R.G., Mitchell J.B., Lisanti M.P., Simone N.L. 2013. Caloric restriction augments radiation efficacy in breast cancer. Cell Cycle. 12, 1955–1963.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Ning Y.-C., Cai G.-Y., Zhuo L., Gao J.-J., Dong D., Cui S.-Y., Shi S.-Z., Feng Z., Zhang L., Sun X.-F., Chen X.-M. 2013. Beneficial effects of short-term calorie restriction against cisplatin-induced acute renal injury in aged rats. Nephron Exp. Nephrol. 124, 19–27.

    Article  CAS  PubMed  Google Scholar 

  139. Safdie F.M., Dorff T., Quinn D., Fontana L., Wei M., Lee C., Cohen P., Longo V.D. 2009. Fasting and cancer treatment in humans: A case series report. Aging (Albany, NY). 1, 988–1007.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Lee C., Raffaghello L., Brandhorst S., Safdie F.M., Bianchi G., Martin-Montalvo A., Pistoia V., Wei M., Hwang S., Merlino A., Emionite L., de Cabo R., Longo V.D. 2012. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci. Transl. Med. 4, 124ra27.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Lee C., Longo V.D. 2011. Fasting vs. dietary restriction in cellular protection and cancer treatment: From model organisms to patients. Oncogene. 30, 3305–3316.

    CAS  PubMed  Google Scholar 

  142. Holloszy J.O., Fontana L. 2007. Caloric restriction in humans. Exp. Gerontol. 42, 709–712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Heilbronn L.K., Smith S.R., Martin C.K., Anton S.D., Ravussin E. 2005. Alternate-day fasting in nonobese subjects: Effects on body weight, body composition, and energy metabolism. Am. J. Clin. Nutr. 81, 69–73.

    CAS  PubMed  Google Scholar 

  144. Barger J.L., Kayo T., Vann J.M., Arias E.B., Wang J., Hacker T.A., Wang Y., Raederstorff D., Morrow J.D., Leeuwenburgh C., Allison D.B., Saupe K.W., Cartee G.D., Weindruch R., Prolla T.A. 2008. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS ONE. 3, e2264.

    Article  CAS  Google Scholar 

  145. Luo J., Solimini N.L., Elledge S.J. 2009. Principles of cancer therapy: Oncogene and non-oncogene addiction. Cell. 136, 823–837.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Magkos F., Yannakoulia M., Chan J.L., Mantzoros C.S. 2009. Management of the metabolic syndrome and type 2 diabetes through lifestyle modification. Annu. Rev. Nutr. 29, 223–256.

    Article  CAS  PubMed  Google Scholar 

  147. Melendez A. 2003. Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science. 301, 1387–1391.

    CAS  PubMed  Google Scholar 

  148. Jia K., Levine B. Autophagy is required for dietary restriction-mediated life span extension in C. elegans. Autophagy. 3, 597–599.

  149. Lozy F., Karantza V. 2012. Autophagy and cancer cell metabolism. Semin. Cell Dev. Biol. 23, 395–401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Maiuri M.C., Tasdemir E., Criollo A., Morselli E., Vicencio J.M., Carnuccio R., Kroemer G. 2008. Control of autophagy by oncogenes and tumor suppressor genes. Cell Death Differ. 16, 87–93.

    Article  PubMed  CAS  Google Scholar 

  151. Lin Z., Fang D. 2013. The roles of SIRT1 in cancer. Genes Cancer. 4, 97–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Park S.-J., Ahmad F., Philp A., Baar K., Williams T., Luo H., Ke H., Rehmann H., Taussig R., Brown A.L., Kim M.K., Beaven M.A., Burgin A.B., Manganiello V., Chung J.H. 2012. Resveratrol ameliorates agingrelated metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell. 148, 421–433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Hubbard B.P., Gomes A.P., Dai H., Li J., Case A.W., Considine T., Riera T.V., Lee J.E., E S.Y., Lamming D.W., Pentelute B.L., Schuman E.R., Stevens L.A., Ling A.J.Y., Armour S.M., Michan S., Zhao H., et al. 2013. Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science. 339, 1216–1219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Lamming D.W., Ye L., Katajisto P., Goncalves M.D., Saitoh M., Stevens D.M., Davis J.G., Salmon A.B., Richardson A., Ahima R.S., Guertin D.A., Sabatini D.M., Baur J.A. 2012. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science. 335, 1638–1643.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Yecies D., Carlson N.E., Deng J., Letai A. 2010. Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1. Blood. 115, 3304–3313.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Basic Medicine, Lomonosov Moscow State University, Moscow, 119991, Russia

    V. V. Senichkin, G. S. Kopeina, A. V. Zamaraev, I. N. Lavrik & B. D. Zhivotovsky

  2. Department of Translational Inflammation Research, Otto von Guericke University, Magdeburg, 39120, Germany

    I. N. Lavrik

  3. Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Stockholm, 17177, Sweden

    B. D. Zhivotovsky

Authors
  1. V. V. Senichkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. S. Kopeina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. V. Zamaraev
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I. N. Lavrik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. D. Zhivotovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B. D. Zhivotovsky.

Additional information

Original Russian Text © V.V. Senichkin, G.S. Kopeina, A.V. Zamaraev, I.N. Lavrik, B.D. Zhivotovsky, 2016, published in Molekulyarnaya Biologiya, 2016, Vol. 50, No. 3, pp. 416–434.

The article was translated by the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Senichkin, V.V., Kopeina, G.S., Zamaraev, A.V. et al. Nutrient restriction in combinatory therapy of tumors. Mol Biol 50, 362–378 (2016). https://doi.org/10.1134/S0026893316030109

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893316030109

Keywords

Search

Navigation