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Advances in Nutrition and Cancer pp 311–323Cite as

A Holistic Approach to Study the Effects of Natural Antioxidants on Inflammation and Liver Cancer

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Part of the book series: Cancer Treatment and Research ((CTAR,volume 159))

Abstract

The limited effectiveness of chemotherapy and the high recurrence rate of cancers highlight the urgent need to identify new molecular targets and to develop new treatments. Numerous epidemiological studies have recently highlighted the existence of an inverse association between fruit and vegetable consumption, natural antioxidants, and cancer risk; in fact, antioxidant intake through diet or supplements of plant origin is strongly recommended for cancer prevention and cure. In general, antioxidants are substances of vegetable, mineral, or animal origin that neutralize free radicals and protect the body from their negative actions on the plasma membrane, proteins, and DNA. Hence, cancer can be prevented by the stimulation of the immune system to destroy cancer cells or to block their proliferation. Since living organisms may be studied as a whole complex system by the “omics sciences” which tend toward understanding and describing the global information of genes, mRNA, proteins, and metabolites, our aim is to use bioinformatics and systems biology to study cytokinome, which plays an important role in the evolution of inflammatory processes and is also a key component in the evolution of cancer, a disease recognized as depending on chronic inflammation and also with the concomitant presence of type 2 diabetes and obesity. On the whole, we define cytokinome as the totality of these proteins and their interactions in and around biological cells. Understanding the complex interaction network of cytokines in patients affected by cancers should be very useful both to follow the evolution of cancer from its early stages and to define innovative therapeutic strategies by using systems biology approaches. In this paper, we review some results of our group in the light of the “omics” logic, and in particular (1) the need for a global approach to study complex systems such as multifactorial cancer and, in particular, hepatocellular carcinoma, (2) the correlation between natural antioxidants, inflammation, and liver cancer, (3) the challenge and significance of the cytokinome profile, (4) the evaluation of the cytokinome profile of patients with type 2 diabetes and/or chronic hepatitis C infection, and (5) adipokine interactome.

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Abbreviations

ACE:

Angiotensin-converting enzyme

ADIPOQ:

Adiponectin

AGT:

Angiotensin II

CHC:

Chronic hepatitis C

CHD:

CHC and type 2 diabetes

CXCL1:

Chemokine (CXC motif) ligand 1

CXCL9:

Chemokine (CXC motif) ligand 9

GIP:

Glucose-dependent insulinotropic peptide

HCC:

Hepatocellular carcinoma

HGF:

Hepatocyte growth factor

IL-1:

Interleukin-1

JAK:

Janus kinase

LC:

CHC-related cirrhosis

LCD:

CHC-related cirrhosis and type 2 diabetes

MIF:

Macrophage migration inhibitory factor

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NGF:

Nerve growth factor

NR3C1:

Nuclear receptor subfamily 3 group C, member 1

PAI-1:

Plasminogen activator inhibitor 1

D (POLR2D):

Polymerase (RNA) II (DNA directed) polypeptide

RBP4:

Retinol binding protein 4

RELA:

V-rel reticuloendotheliosis viral oncogene homolog A

ROS:

Reactive oxygen species

SFR5:

Secreted frizzled-related protein 5

STAT3:

signal transducer and activator of transcription

T2D:

Type 2 diabetes

TNF:

Tumor necrosis factor

USF1:

Upstream stimulatory factor 1

References

  1. Carlsen MH, Halvorsen BL, Holte K et al (2010) The total antioxidant content of more than 3,100 foods, beverages, spices, herbs and supplements used worldwide. Nutr J 9:3

    Article  PubMed  Google Scholar 

  2. Das Sarma A, Rahaman Mallick A, Ghosh AK (2010) Free radicals and their role in different clinical conditions: an overview. Int J Pharma Sci Res 1:185–192

    CAS  Google Scholar 

  3. Agewall S, Wright S, Doughty RN et al (2000) Does a glass of red wine improve endothelial function? Eur Heart J 21:74–78

    Article  PubMed  CAS  Google Scholar 

  4. Zhang Y, Shen G, Yu Y et al (2009) The hormetic effect of cadmium on the activity of antioxidant enzymes in the earthworm Eisenia fetida. Environ Pollut 157:3064–3068

    Article  PubMed  CAS  Google Scholar 

  5. Seyfried T, Shelton LM (2010) Cancer as a metabolic disease. Nutr Metab 7:7

    Article  Google Scholar 

  6. Gonzaga-Jauregui C, Lupski JR, Gibbs RA (2012) Human genome sequencing in health and disease. Annu Rev Med 63:35–61

    Article  PubMed  CAS  Google Scholar 

  7. Costantini S, Autiero I, Colonna G (2008) On new challenge for the bioinformatics. Bioinformation 3:238–239

    Article  PubMed  Google Scholar 

  8. Castello G, Costantini S, Scala S (2010) Targeting the inflammation in HCV-associated hepatocellular carcinoma: a role in the prevention and treatment. J Trasl Med 8:109

    Article  Google Scholar 

  9. Costantini S, Capone F, Guerriero E et al (2012) Cytokinome profile of patients with type 2 diabetes and/or chronic hepatitis C infection. PLoS ONE 7(6):e39486

    Article  PubMed  CAS  Google Scholar 

  10. Palladino P, Portella L, Colonna G et al (2012) The N-terminal peptide of CXCL11 as structural template for CXCR3 antagonist: synthesis, conformational analysis and binding studies. Chem Biol Drug Des 80(2):254–265

    Article  PubMed  CAS  Google Scholar 

  11. Trotta T, Costantini S, Colonna G (2009) Modelling of the membrane receptor CXCR3 and its complexes with CXCL9, CXCL10 and CXCL11 chemokines: putative target for new drug design. Mol Immunol 47:332–339

    Article  PubMed  CAS  Google Scholar 

  12. Capone F, Costantini S, Guerriero E et al (2010) Serum cytokine levels in patients with hepatocellular carcinoma. Eur Cytokine Netw 21:99–104

    PubMed  CAS  Google Scholar 

  13. Costantini S, Capone F, Guerriero E et al (2010) Serum cytokine levels as putative prognostic markers in the progression of chronic HCV hepatitis to cirrhosis. Eur Cytokine Netw 21:251–256

    PubMed  CAS  Google Scholar 

  14. Costantini S, Castello G, Colonna G (2010) Human Cytokinome: a new challenge for systems biology. Bioinformation 5(4):166–167

    Article  PubMed  Google Scholar 

  15. Huang JF, Dai CY, Hwang SJ et al (2007) Hepatitis C viremia increases the association with type 2 diabetes mellitus in a hepatitis B and C endemic area: an epidemiological link with virological implication. Am J Gastroenterol 102:1237–1243

    Article  PubMed  Google Scholar 

  16. Hung CH, Lee CM, Wang JH et al (2011) Impact of diabetes mellitus on incidence of hepatocellular carcinoma in chronic hepatitis C patients treated with interferon-based antiviral therapy. Int J Cancer 128(10):2344–2352

    Article  PubMed  CAS  Google Scholar 

  17. Carvalheira JBC, Siloto RMP, Ignacchitti I et al (2001) Insulin modulates leptin-induced STAT3 activation in rat hypothalamus. FEBS Lett 500:119–124

    Article  PubMed  CAS  Google Scholar 

  18. Ho HH, Ivashkiv LB (2006) Role of STAT3 in type I interferon responses. JBC 281:14111–14118

    Article  CAS  Google Scholar 

  19. Hollenberg SM, Weinberger C, Ong ES et al (1985) Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature 318:635–641

    Article  PubMed  CAS  Google Scholar 

  20. Takahara Y, Takahashi M, Zhang Q-W et al (2008) Serial changes in expression of functionally clustered genes in progression of liver fibrosis in hepatitis C patients. World J Gastroenterol 14:2010–2022

    Article  PubMed  CAS  Google Scholar 

  21. Gentile A, Trusolino L, Comoglio PM (2008) The met tyrosine kinase receptor in development and cancer. Cancer Metastasis Rev 27:85–94

    Article  PubMed  CAS  Google Scholar 

  22. Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556

    Article  PubMed  CAS  Google Scholar 

  23. Raucci R, Rusolo F, Sharma A et al (2012) Functional and structural features of adipokine family. Cytokine

    Google Scholar 

  24. Scardoni G, Petterlini M, Laudanna C (2009) Analyzing biological network parameters with CentiScaPe. Bioinformatics 25:2857–2859

    Article  PubMed  CAS  Google Scholar 

  25. Yu H, Kim PM, Sprecher E et al (2007) The importance of bottlenecks in protein networks: correlation with gene essentiality and expression dynamics. PLoS Comput Biol 3:e59

    Article  PubMed  Google Scholar 

  26. Brandes U (2001) A faster algorithm for betweenness centrality. J Math Sociol 25:163–177

    Article  Google Scholar 

  27. Sharma A, Gautam V, Costantini S et al (2012) Interactomic and pharmacological insights on human Sirt-1. Front Exp Pharmacol Drug Discov 3:40

    Google Scholar 

  28. Jayaprakasam BJ, Vanisree M, Zhang Y et al (2006) Impact of alkyl esters of caffeic and ferulic acids on tumor cell proliferation cyclooxygenase enzyme and lipid peroxidation. J Agric Food Chem 54:5375–5381

    Article  PubMed  CAS  Google Scholar 

  29. Lin HP, Kuo LK, Chuu CP et al (2012) Combined treatment of curcumin and small molecule inhibitors suppresses proliferation of A549 and H1299 human non-small-cell lung cancer cells. Phytother Res 26:122–126

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione Giovanni Pascale–IRCCS-Italia, Via Ammiraglio Bianco, 83013, Mercogliano, AV, Italy

    Susan Costantini & Giuseppe Castello

  2. Department of Biochemistry, Biophysics and General Pathology (Second University of Naples), via Costantinopoli 16, 80138, Naples, Italy

    Giovanni Colonna

Authors
  1. Susan Costantini
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  2. Giovanni Colonna
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  3. Giuseppe Castello
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Corresponding authors

Correspondence to Susan Costantini or Giovanni Colonna .

Editor information

Editors and Affiliations

  1. Dept. of Biochemistry and Biophysics, Second University of Naples, Naples, Italy

    Vincenzo Zappia

  2. Clinical and Experimental Medicine, University of Naples "Federico II", Naples, Italy

    Salvatore Panico

  3. Institute of Food Sciences National Research Council, Avellino, Italy

    Gian Luigi Russo

  4. Dept. of Experimental Oncology, National Cancer Institute, Naples, Italy

    Alfredo Budillon

  5. Dept. of Biochemistry and Biophysics, Second University of Naples, Naples, Italy

    Fulvio Della Ragione

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© 2014 Springer-Verlag Berlin Heidelberg

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Costantini, S., Colonna, G., Castello, G. (2014). A Holistic Approach to Study the Effects of Natural Antioxidants on Inflammation and Liver Cancer. In: Zappia, V., Panico, S., Russo, G., Budillon, A., Della Ragione, F. (eds) Advances in Nutrition and Cancer. Cancer Treatment and Research, vol 159. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38007-5_18

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  • DOI: https://doi.org/10.1007/978-3-642-38007-5_18

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-38006-8

  • Online ISBN: 978-3-642-38007-5

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