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Modulation of Tumor Immunity by Medicinal Plant or Functional Food-Derived Compounds

  • Robert E. WrightIII
  • Nirmal Joshee
  • Prahlad ParajuliEmail author
Chapter

Abstract

Most forms of conventional cancer treatments are accompanied by undesirable side effects. Moreover, due to tumor heterogeneity, resistance to treatment and subsequent recurrence is often inevitable. Therefore, there is a need for development of progressive forms of adjuvant therapeutics. The tumor micro-environment is composed of tumor cells and multiple stromal cell types, including immune cells, many of which can produce pro-tumor chemokines and cytokines. The production of these molecules can result in a cascade effect, signaling other cells to promote an anti-cytotoxic, pro-tumor inflammatory response which hinders the necessary immune response needed to eliminate neoplastic cells. The pro-tumor inflammatory response is a key component during the progressive development of cancer. The “hijacking” of the immune system in the tumor environment provides a target which can be used to revert the immune system back to a type 1, pro-cytotoxic response. Natural compounds found in many traditional foods and medicines have a proven history of being anti-inflammatory, a key component which can be utilized during cancer treatment. Application of specific natural compounds in conjunction with conventional medicine can provide an additional level of support via modulation of the immune system. Phytochemicals found in turmeric, soy, and Scutellaria have shown profound effects on attenuating and modulating inflammation. This chapter looks into the mechanism of action and prospects for using these phytochemicals as an immune-modulatory adjuvant in the treatment of cancer.

Keywords

Turmeric Soy Scutellaria Immune modulation Cancer 

References

  1. Abernathy LM et al (2015) Soy isoflavones promote radioprotection of normal lung tissue by inhibition of radiation-induced activation of macrophages and neutrophils. J Thorac Oncol 10(12):1703–1712PubMedCrossRefPubMedCentralGoogle Scholar
  2. Abernathy LM et al (2017) Innate immune pathways associated with lung radioprotection by soy isoflavones. Front Oncol 7:7PubMedPubMedCentralCrossRefGoogle Scholar
  3. Anthony RM et al (2007) Protective immune mechanisms in helminth infection. Nat Rev Immunol 7(12):975–987PubMedPubMedCentralCrossRefGoogle Scholar
  4. Banerjee S et al (2008) Multi-targeted therapy of cancer by genistein. Cancer Lett 269(2):226–242PubMedPubMedCentralCrossRefGoogle Scholar
  5. Bharti AC et al (2003) Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor–κB and IκBα kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood 101(3):1053PubMedCrossRefPubMedCentralGoogle Scholar
  6. Bickel MM (1993) The role of interleukin-8 in inflammation and mechanisms of regulation. J Periodontol 64(5 suppl):456–460PubMedPubMedCentralGoogle Scholar
  7. Bradley JR (2008) TNF-mediated inflammatory disease. J Pathol 214(2):149–160PubMedCrossRefPubMedCentralGoogle Scholar
  8. Brouet I, Ohshima H (1995) Curcumin, an anti-tumor promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem Biophys Res Commun 206(2):533–540PubMedCrossRefPubMedCentralGoogle Scholar
  9. Chang A (2011) Chemotherapy, chemoresistance and the changing treatment landscape for NSCLC. Lung Cancer 71(1):3–10PubMedCrossRefPubMedCentralGoogle Scholar
  10. Charles A, Janeway JARM (2002) Innate immune recognition. Annu Rev Immunol 20:197–216CrossRefGoogle Scholar
  11. Charlton B, Lafferty KJ (1995) The Th1/Th2 balance in autoimmunity. Curr Opin Immunol 7(6):793–798PubMedCrossRefPubMedCentralGoogle Scholar
  12. Choi J-S et al (2004) Flavones mitigate tumor necrosis factor-α-induced adhesion molecule upregulation in cultured human endothelial cells: role of nuclear factor-κB. J Nutr 134(5):1013–1019PubMedCrossRefPubMedCentralGoogle Scholar
  13. Cortez-Retamozo V et al (2012) Origins of tumor-associated macrophages and neutrophils. Proc Natl Acad Sci U S A 109(7):2491–2496PubMedPubMedCentralCrossRefGoogle Scholar
  14. Damsker JM, Hansen AM, Caspi RR (2010) Th1 and Th17 cells: adversaries and collaborators. Ann N Y Acad Sci 1183:211–221PubMedPubMedCentralCrossRefGoogle Scholar
  15. Dandawate S et al (2012) Scutellaria extract and wogonin inhibit tumor-mediated induction of T(reg) cells via inhibition of TGF-β1 activity. Cancer Immunol Immunother 61(5):701–711PubMedCrossRefPubMedCentralGoogle Scholar
  16. Davis JN, Kucuk O, Sarkar FH (1999) Genistein inhibits NF-kB activation in prostate cancer cells. Nutr Cancer 35(2):167–174PubMedCrossRefPubMedCentralGoogle Scholar
  17. Fan Y, Mao R, Yang J (2013) NF-κB and STAT3 signaling pathways collaboratively link inflammation to cancer. Protein Cell 4(3):176–185PubMedPubMedCentralCrossRefGoogle Scholar
  18. Fernandez de Simon B et al (1992) Importance of phenolic compounds for the characterization of fruit juices. J Agric Food Chem 40(9):1531–1535CrossRefGoogle Scholar
  19. Fridlender ZG, Albelda SM (2012) Tumor-associated neutrophils: friend or foe? Carcinogenesis 33(5):949–955PubMedCrossRefPubMedCentralGoogle Scholar
  20. Fridlender ZG et al (2009) Polarization of tumor-associated neutrophil (TAN) phenotype by TGF-β: “N1” versus “N2” TAN. Cancer Cell 16(3):183–194PubMedPubMedCentralCrossRefGoogle Scholar
  21. Garg AD, Dudek AM, Agostinis P (2013) Cancer immunogenicity, danger signals, and DAMPs: what, when, and how? Biofactors 39(4):355–367PubMedCrossRefPubMedCentralGoogle Scholar
  22. Gong L et al (2003) Inactivation of NF-κB by genistein is mediated via Akt signaling pathway in breast cancer cells. Oncogene 22(30):4702–4709PubMedCrossRefPubMedCentralGoogle Scholar
  23. Gota VS et al (2010) Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J Agric Food Chem 58(4):2095–2099PubMedCrossRefPubMedCentralGoogle Scholar
  24. Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140(6):883–899PubMedPubMedCentralCrossRefGoogle Scholar
  25. Hayden MSMSG (2004) Signaling to NF-κB. Genes Dev 18(18):2195–2224PubMedCrossRefPubMedCentralGoogle Scholar
  26. Hehlgans T, Pfeffer K (2005) The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunology 115(1):1–20PubMedPubMedCentralCrossRefGoogle Scholar
  27. Hoesel B, Schmid JA (2013) The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer 12:86–86PubMedPubMedCentralCrossRefGoogle Scholar
  28. Hussain F, Sandeep M, Joshee N, Parajuli P (2016) Application of bioactive compounds from Scutellaria in neurologic disorders. In: The benefits of natural products for neurodegenerative diseases. Springer, Basel, pp 79–93CrossRefGoogle Scholar
  29. Janeway CAC (1989) The priming of helper T cells. Semin Immunol 1(1):13–20PubMedPubMedCentralGoogle Scholar
  30. Janssen K et al (1998) Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study. Am J Clin Nutr 67(2):255–262PubMedCrossRefPubMedCentralGoogle Scholar
  31. Kaiko GE et al (2008) Immunological decision-making: how does the immune system decide to mount a helper T-cell response? Immunology 123(3):326–338PubMedPubMedCentralCrossRefGoogle Scholar
  32. Kan X et al (2017) Scutellaria barbata D. Don extract inhibits the tumor growth through down-regulating of Treg cells and manipulating Th1/Th17 immune response in hepatoma H22-bearing mice. BMC Complement Altern Med 17:41PubMedPubMedCentralCrossRefGoogle Scholar
  33. Kolaczkowska E, Kubes P (2013) Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 13(3):159–175PubMedCrossRefPubMedCentralGoogle Scholar
  34. Kwon Y (2014) Effect of soy isoflavones on the growth of human breast tumors: findings from preclinical studies. Food Sci Nutr 2(6):613–622PubMedPubMedCentralCrossRefGoogle Scholar
  35. Lacy P (2006) Mechanisms of degranulation in neutrophils. Allergy, Asthma Clin Immunol 2(3):98–108CrossRefGoogle Scholar
  36. Lafaille JJ (1998) The role of helper T cell subsets in autoimmune diseases. Cytokine Growth Factor Rev 9(2):139–151PubMedCrossRefPubMedCentralGoogle Scholar
  37. Lee ASJLYS (2013) Curcumin in various cancers. Biofactors 39(1):56–68PubMedCrossRefPubMedCentralGoogle Scholar
  38. Lemberkovics E (1998) Phytochemical evaluation of essential oils, medicinal plants and their preparations. Acta Pharm Hung 68(3):141–149PubMedPubMedCentralGoogle Scholar
  39. Lesinski GB et al (2015) Consumption of soy isoflavone enriched bread in men with prostate cancer is associated with reduced pro-inflammatory cytokines and immune suppressive cells. Cancer Prevent Res 8(11):1036–1044CrossRefGoogle Scholar
  40. Li YY (2002) Down-regulation of invasion and angiogenesis-related genes identified by cDNA microarray analysis of PC3 prostate cancer cells treated with genistein. Cancer Lett 186(2):157–164PubMedCrossRefPubMedCentralGoogle Scholar
  41. Liang Y-C et al (1999) Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages. Carcinogenesis 20(10):1945–1952PubMedCrossRefPubMedCentralGoogle Scholar
  42. Lotze MT et al (2007) The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity. Immunol Rev 220(1):60–81PubMedCrossRefPubMedCentralGoogle Scholar
  43. Lu Y-C, Yeh W-C, Ohashi PS (2008) LPS/TLR4 signal transduction pathway. Cytokine 42(2):145–151PubMedCrossRefPubMedCentralGoogle Scholar
  44. MacEwan DJ (2002) TNF ligands and receptors – a matter of life and death. Br J Pharmacol 135(4):855–875PubMedPubMedCentralCrossRefGoogle Scholar
  45. Mantovani A et al (2008) Cancer-related inflammation. Nature 454:436+PubMedCrossRefPubMedCentralGoogle Scholar
  46. Martinez FO, Gordon S (2014) The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 6:13PubMedPubMedCentralCrossRefGoogle Scholar
  47. Mayadas TN, Cullere X, Lowell CA (2014) The multifaceted functions of neutrophils. Annu Rev Pathol 9:181–218PubMedCrossRefPubMedCentralGoogle Scholar
  48. Messina M, Badger TM (2017) Health effects of isoflavones misrepresented. Food Chem 225:289–292PubMedCrossRefPubMedCentralGoogle Scholar
  49. Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8(12):958–969PubMedPubMedCentralCrossRefGoogle Scholar
  50. Moudi M et al (2013) Vinca alkaloids. Int J Prev Med 4(11):1231–1235PubMedPubMedCentralGoogle Scholar
  51. Newton K, Dixit VM (2012) Signaling in innate immunity and inflammation. Cold Spring Harb Perspect Biol 4(3):a006049PubMedPubMedCentralCrossRefGoogle Scholar
  52. Nielsen SE et al (2007) Effect of parsley (Petroselinum crispum) intake on urinary apigenin excretion, blood antioxidant enzymes and biomarkers for oxidative stress in human subjects. Br J Nutr 81(6):447–455CrossRefGoogle Scholar
  53. Norn SS (2009) From willow bark to acetylsalicylic acid. Dan Medicinhist Arbog 37:79–98PubMedPubMedCentralGoogle Scholar
  54. Oberley TD (2002) Oxidative damage and cancer. Am J Pathol 160(2):403–408PubMedPubMedCentralCrossRefGoogle Scholar
  55. Parajuli P et al (2011) Delayed growth of glioma by Scutellaria flavonoids involve inhibition of Akt, GSK-3 and NF-κB signaling. J Neuro-Oncol 101(1):15–24CrossRefGoogle Scholar
  56. Parameswaran N, Patial S (2010) Tumor necrosis factor-α signaling in macrophages. Crit Rev Eukaryot Gene Expr 20(2):87–103PubMedPubMedCentralCrossRefGoogle Scholar
  57. Patil RH et al (2016) Anti-inflammatory effect of apigenin on LPS-induced pro-inflammatory mediators and AP-1 factors in human lung epithelial cells. Inflammation 39(1):138–147PubMedCrossRefPubMedCentralGoogle Scholar
  58. Pavese JM, Farmer RL, Bergan RC (2010) Inhibition of cancer cell invasion and metastasis by genistein. Cancer Metastasis Rev 29(3):465–482PubMedPubMedCentralCrossRefGoogle Scholar
  59. Peng YY (2014) Immune and anti-oxidant functions of ethanol extracts of Scutellaria baicalensis Georgi in mice bearing U14 cervical cancers. Asian Pac J Cancer Prev 15(10):4129–4133PubMedCrossRefPubMedCentralGoogle Scholar
  60. Pilaro AM et al (1994) TNF-alpha is a principal cytokine involved in the recruitment of NK cells to liver parenchyma. J Immunol 153(1):333PubMedPubMedCentralGoogle Scholar
  61. Prasad S, Aggarwal B (2011) Turmeric, the golden spice: from traditional medicine to modern medicine. In: Wachtel-Galor S, Benzie FF (eds) Herbal medicine: biomolecular and clinical aspects. CRC Press/Taylor & Francis, Boca RatonGoogle Scholar
  62. Rath PCP (1999) TNF-induced signaling in apoptosis. J Clin Immunol 19(6):350–364PubMedCrossRefPubMedCentralGoogle Scholar
  63. Reuter S et al (2010) Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 49(11):1603–1616PubMedPubMedCentralCrossRefGoogle Scholar
  64. Roach JC et al (2005) The evolution of vertebrate toll-like receptors. Proc Natl Acad Sci U S A 102(27):9577–9582PubMedPubMedCentralCrossRefGoogle Scholar
  65. Sabroe I et al (2008) The role of TLR activation in inflammation. J Pathol 214(2):126–135PubMedCrossRefPubMedCentralGoogle Scholar
  66. Sandur SK et al (2007) Role of prooxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane). Free Radic Biol Med 43(4):568–580PubMedPubMedCentralCrossRefGoogle Scholar
  67. Singer AJ, Clark RAF (1999) Cutaneous wound healing. N Engl J Med 341(10):738–746PubMedCrossRefPubMedCentralGoogle Scholar
  68. Singh S, Aggarwal BB (1995) Activation of transcription factor NF-κB is suppressed by curcumin (diferuloylmethane). J Biol Chem 270(42):24995–25000PubMedCrossRefPubMedCentralGoogle Scholar
  69. Storka A, Vcelar B, Klickovic U, Gouya G, Weisshaar S, Aschauer S, Bolger G, Helson L, Wolzt M (2015) Safety, tolerability and pharmacokinetics of liposomal curcumin in healthy humans. Int J Clin Pharmacol Ther 53:54–65PubMedCrossRefPubMedCentralGoogle Scholar
  70. Surh Y-J et al (2001) Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-κB activation. Mutat Res 480–481:243–268PubMedCrossRefPubMedCentralGoogle Scholar
  71. Takeuchi Y, Nishikawa H (2016) Roles of regulatory T cells in cancer immunity. Int Immunol 28(8):401–409PubMedPubMedCentralCrossRefGoogle Scholar
  72. Tang D et al (2012) PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunol Rev 249(1):158–175PubMedPubMedCentralCrossRefGoogle Scholar
  73. Testa JR, Tsichlis PN (2005) AKT signaling in normal and malignant cells. Oncogene 24(50):7391–7393PubMedCrossRefPubMedCentralGoogle Scholar
  74. Thoppil RJ, Bishayee A (2011) Terpenoids as potential chemopreventive and therapeutic agents in liver cancer. World J Hepatol 3(9):228–249PubMedPubMedCentralCrossRefGoogle Scholar
  75. Tsan M-F (2006) Toll-like receptors, inflammation and cancer. Semin Cancer Biol 16(1):32–37PubMedCrossRefPubMedCentralGoogle Scholar
  76. Vivier E et al (2008) Functions of natural killer cells. Nat Immunol 9(5):503–510PubMedCrossRefPubMedCentralGoogle Scholar
  77. Wang J et al (2008) Genistein inhibits the development of atherosclerosis via inhibiting NF-κB and VCAM-1 expression in LDLR knockout mice. Can J Physiol Pharmacol 86(11):777–784PubMedCrossRefPubMedCentralGoogle Scholar
  78. Wang N, Liang H, Zen K (2014a) Molecular mechanisms that influence the macrophage M1–M2 polarization balance. Front Immunol 5:614PubMedPubMedCentralGoogle Scholar
  79. Wang J et al (2014b) Anti-inflammatory effects of Apigenin in lipopolysaccharide-induced inflammatory in acute lung injury by suppressing COX-2 and NF-kB pathway. Inflammation 37(6):2085–2090PubMedCrossRefPubMedCentralGoogle Scholar
  80. Waugh DJJ, Wilson C (2008) The interleukin-8 pathway in cancer. Clin Cancer Res 14(21):6735PubMedCrossRefPubMedCentralGoogle Scholar
  81. Wong CK et al (2001) Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-γ, IL-4, IL-10 and IL-13) in patients with allergic asthma. Clin Exp Immunol 125(2):177–183PubMedPubMedCentralCrossRefGoogle Scholar
  82. Wu JJ (2003) Natural killer cells and cancer. Adv Cancer Res 90:127–156PubMedCrossRefPubMedCentralGoogle Scholar
  83. Xu B, Yu L, Zhao L-Z (2017) Curcumin up regulates T helper 1 cells in patients with colon cancer. Am J Transl Res 9(4):1866–1875PubMedPubMedCentralGoogle Scholar
  84. Yuan Zhang YZ, Gu W, Sun B (2014) Th1/Th2 cell differentiation and molecular signals. In: Sun B (ed) T helper cell differentiation and their function. Springer, Berlin, pp 15–34Google Scholar
  85. Zhang J-M, An J (2007) Cytokines, inflammation and pain. Int Anesthesiol Clin 45(2):27–37PubMedPubMedCentralCrossRefGoogle Scholar
  86. Zhang X et al (2014) Flavonoid Apigenin inhibits lipopolysaccharide-induced inflammatory response through multiple mechanisms in macrophages. PLoS One 9(9):e107072PubMedPubMedCentralCrossRefGoogle Scholar
  87. Zhou XX (2014) Genistein antagonizes inflammatory damage induced by β-amyloid peptide in microglia through TLR4 and NF-κB. Nutrition 30(1):90–95PubMedCrossRefPubMedCentralGoogle Scholar
  88. Zubair H et al (2017) Cancer chemoprevention by phytochemicals: Nature’s healing touch. Molecules 22(3):E395PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Robert E. WrightIII
    • 1
  • Nirmal Joshee
    • 2
  • Prahlad Parajuli
    • 1
    Email author
  1. 1.Wayne State University School of MedicineDetroitUSA
  2. 2.Agricultural Research Station, College of AgricultureFamily Sciences and Technology, Fort Valley State UniversityFort ValleyUSA

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