Skip to main content
SpringerLink
Log in

Proteins with Anticancer and Antimicrobial Activities from Mammals, Submammalian Vertebrates and Invertebrates

  • Chapter
  • First Online:
Antitumor Potential and other Emerging Medicinal Properties of Natural Compounds

  • 1657 Accesses

Abstract

The intent of this chapter is to review proteins with anticancer and antimicrobial activities from various animal species. The proteins comprise venom proteins from snakes, scorpions, and bees; peptides from frogs and toads; bovine pancreas and frogs; and mammalian proteins and peptides including lactoferrin, cathelicidins, tumor necrosis factor, interferons, interleukins, and hormonal peptides. To avoid duplication of efforts, the medicinal applications of mammalian lectins and ribonucleases fall in the realm of other chapters in this book. The current progress and future work on animal constituents with medicinal activity depicted in this chapter would help to shed light on their clinical potentials or applications.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Sheng-Ji P (2001) Ethnobotanical approaches of traditional medicine studies: some experiences from Asia. Pharm Biol 39(Suppl 1):74–79

    PubMed  Google Scholar 

  2. Klotman ME, Chang TL (2006) Defensins in innate antiviral immunity. Nat Rev Immunol 6:447–456

    Article  PubMed  CAS  Google Scholar 

  3. Sorensen OE, Follin P, Johnsen AH, Calafat J, Tjabringa GS, Hiemstra PS et al (2001) Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood 97:3951–3959

    Article  PubMed  CAS  Google Scholar 

  4. Meyer JE, Harder J (2007) Antimicrobial peptides in oral cancer. Curr Pharm Des 13:3119–3130

    Article  PubMed  CAS  Google Scholar 

  5. Coffelt SB, Marini FC, Watson K, Zwezdaryk KJ, Dembinski JL, LaMarca HL et al (2009) The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells. Proc Natl Acad Sci U S A 106:3806–3811

    Article  PubMed  CAS  Google Scholar 

  6. Zanetti M, Gennaro R, Romeo D (1995) Cathelicidins: a novel protein family with a common proregion and a variable C-terminal antimicrobial domain. FEBS Lett 374:1–5

    Article  PubMed  CAS  Google Scholar 

  7. Wong CC, Zhang L, Li ZJ, Wu WK, Ren SX, Chen YC et al (2012) Protective effects of cathelicidin-encoding Lactococcus lactis in murine ulcerative colitis. J Gastroenterol Hepatol 27:1205–1212

    Article  PubMed  CAS  Google Scholar 

  8. Wong JH, Ng TB, Legowska A, Rolka K, Hui M, Cho CH (2011) Antifungal action of human cathelicidin fragment (LL13-37) on Candida albicans. Peptides 32:1996–2002

    Article  PubMed  CAS  Google Scholar 

  9. Wong JH, Legowska A, Rolka K, Ng TB, Hui M, Cho CH et al (2011) Effects of cathelicidin and its fragments on three key enzymes of HIV-1. Peptides 32:1117–1122

    Article  PubMed  CAS  Google Scholar 

  10. Chuang CM, Monie A, Wu A, Mao CP, Hung CF (2009) Treatment with LL-37 peptide enhances antitumor effects induced by CpG oligodeoxynucleotides against ovarian cancer. Hum Gene Ther 20:303–313

    Article  PubMed  CAS  Google Scholar 

  11. Buchau AS, Morizane S, Trowbridge J, Schauber J, Kotol P, Bui JD et al (2010) The host defense peptide cathelicidin is required for NK cell-mediated suppression of tumor growth. J Immunol 184:369–378

    Article  PubMed  Google Scholar 

  12. Tran D, Tran PA, Tang YQ, Yuan J, Cole T, Selsted ME (2002) Homodimeric theta-defensins from rhesus macaque leukocytes: isolation, synthesis, antimicrobial activities, and bacterial binding properties of the cyclic peptides. J Biol Chem 277:3079–3084

    Article  PubMed  CAS  Google Scholar 

  13. Mader JS, Hoskin DW (2006) Cationic antimicrobial peptides as novel cytotoxic agents for cancer treatment. Expert Opin Investig Drugs 15:933–946

    Article  PubMed  CAS  Google Scholar 

  14. Zhang L, Yu W, He T, Yu J, Caffrey RE, Dalmasso EA et al (2002) Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science 298:995–1000

    Article  PubMed  CAS  Google Scholar 

  15. Zhang L, Lopez P, He T, Yu W, Ho DD (2004) Retraction of an interpretation. Science 303:467

    Article  PubMed  CAS  Google Scholar 

  16. Gounder AP, Wiens ME, Wilson SS, Lu W, Smith JG (2012) Critical determinants of human alpha-defensin 5 activity against non-enveloped viruses. J Biol Chem 287:24554–24562

    Article  PubMed  CAS  Google Scholar 

  17. Chu H, Pazgier M, Jung G, Nuccio SP, Castillo PA, de Jong MF et al (2012) Human alpha-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets. Science 337:477–481

    Article  PubMed  CAS  Google Scholar 

  18. Spudy B, Sonnichsen FD, Waetzig GH, Grotzinger J, Jung S (2012) Identification of structural traits that increase the antimicrobial activity of a chimeric peptide of human beta-defensins 2 and 3. Biochem Biophys Res Commun 427:207–211

    Article  PubMed  CAS  Google Scholar 

  19. Johnstone SA, Gelmon K, Mayer LD, Hancock RE, Bally MB (2000) In vitro characterization of the anticancer activity of membrane-active cationic peptides. I. Peptide-mediated cytotoxicity and peptide-enhanced cytotoxic activity of doxorubicin against wild-type and p-glycoprotein over-expressing tumor cell lines. Anticancer Drug Des 15:151–160

    PubMed  CAS  Google Scholar 

  20. Iwasaki T, Ishibashi J, Tanaka H, Sato M, Asaoka A, Taylor D et al (2009) Selective cancer cell cytotoxicity of enantiomeric 9-mer peptides derived from beetle defensins depends on negatively charged phosphatidylserine on the cell surface. Peptides 30:660–668

    Article  PubMed  CAS  Google Scholar 

  21. Yang X, Dong L, Lv L, Yan X, Lai R, Liu R (2012) A beta-defensin 1-like antimicrobial peptide from the tree shrew. Tupaia belangeri. Gene 509:258–262

    Article  CAS  Google Scholar 

  22. Vogel HJ (2012) Lactoferrin, a bird’s eye view. Biochemistry and cell biology. Biochimie et biologie cellulaire 90:233–244

    Article  PubMed  CAS  Google Scholar 

  23. Mohan KV, Gunasekaran P, Varalakshmi E, Hara Y, Nagini S (2007) In vitro evaluation of the anticancer effect of lactoferrin and tea polyphenol combination on oral carcinoma cells. Cell Biol Int 31:599–608

    Article  PubMed  CAS  Google Scholar 

  24. Varadhachary A, Wolf JS, Petrak K, O’Malley BW Jr, Spadaro M, Curcio C et al (2004) Oral lactoferrin inhibits growth of established tumors and potentiates conventional chemotherapy. Int J Cancer. Journal International du Cancer 111:398–403

    Article  CAS  Google Scholar 

  25. Parodi PW (2007) A role for milk proteins and their peptides in cancer prevention. Curr Pharm Des 13:813–828

    Article  PubMed  CAS  Google Scholar 

  26. Xu XX, Jiang HR, Li HB, Zhang TN, Zhou Q, Liu N (2010) Apoptosis of stomach cancer cell SGC-7901 and regulation of Akt signaling way induced by bovine lactoferrin. J Dairy Sci 93:2344–2350

    Article  PubMed  CAS  Google Scholar 

  27. Jonasch E, Stadler WM, Bukowski RM, Hayes TG, Varadhachary A, Malik R et al (2008) Phase 2 trial of talactoferrin in previously treated patients with metastatic renal cell carcinoma. Cancer 113:72–77

    Article  PubMed  CAS  Google Scholar 

  28. Ammendolia MG, Agamennone M, Pietrantoni A, Lannutti F, Siciliano RA, De Giulio B et al (2012) Bovine lactoferrin-derived peptides as novel broad-spectrum inhibitors of influenza virus. Pathog Glob Health 106:12–19

    Article  PubMed  CAS  Google Scholar 

  29. Mishra B, Leishangthem GD, Gill K, Singh AK, Das S, Singh K, Xess I, Dinda A, Kapil A, Patro IK, Dey S (2013) A novel antimicrobial peptide derived from modified N-terminal domain of bovine lactoferrin: design, synthesis, activity against multidrug-resistant bacteria and Candida. Biochim Biophys Acta 1828:677–686

    Article  PubMed  CAS  Google Scholar 

  30. Haney EF, Nazmi K, Bolscher JG, Vogel HJ (2012) Influence of specific amino acid side-chains on the antimicrobial activity and structure of bovine lactoferrampin. Biochemistry and cell biology (Biochimie et Biologie Cellulaire) 90:362–377

    Article  PubMed  CAS  Google Scholar 

  31. Dranoff G (2004) Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer 4:11–22

    Article  PubMed  CAS  Google Scholar 

  32. Fang EF, Wong JH, Ng TB (2010) Thermostable Kunitz trypsin inhibitor with cytokine inducing, antitumor and HIV-1 reverse transcriptase inhibitory activities from Korean large black soybeans. J Biosci Bioeng 109:211–217

    Article  PubMed  CAS  Google Scholar 

  33. Leonard WJ (2001) Cytokines and immunodeficiency diseases. Nat Rev Immunol 1:200–208

    Article  PubMed  CAS  Google Scholar 

  34. Safai B, Bason M, Friedman-Birnbaum R, Nisce L (1990) Interferon in the treatment of AIDS-associated Kaposi’s sarcoma: the American experience. J Invest Dermatol 95:166S–169S

    Article  PubMed  CAS  Google Scholar 

  35. Bekisz J, Baron S, Balinsky C, Morrow A, Zoon KC (2010) Anti-proliferative properties of Type I and Type II interferon. Pharmaceuticals 3:994–1015

    Article  PubMed  CAS  Google Scholar 

  36. Helson L, Green S, Carswell E, Old LJ (1975) Effect of tumour necrosis factor on cultured human melanoma cells. Nature 258:731–732

    Article  PubMed  CAS  Google Scholar 

  37. van Horssen R, Ten Hagen TL, Eggermont AM (2006) TNF-alpha in cancer treatment: molecular insights, antitumor effects, and clinical utility. Oncologist 11:397–408

    Article  PubMed  Google Scholar 

  38. Brocker C, Thompson D, Matsumoto A, Nebert DW, Vasiliou V (2010) Evolutionary divergence and functions of the human interleukin (IL) gene family. Human Genomics 5:30–55

    Article  PubMed  CAS  Google Scholar 

  39. Mezo G, Manea M (2010) Receptor-mediated tumor targeting based on peptide hormones. Expert Opin Drug Deliv 7:79–96

    Article  PubMed  CAS  Google Scholar 

  40. Saba SR, Vesely DL (2006) Cardiac natriuretic peptides: hormones with anticancer effects that localize to nucleus, cytoplasm, endothelium, and fibroblasts of human cancers. Histol Histopathol 21:775–783

    PubMed  CAS  Google Scholar 

  41. Debruyne F, Bhat G, Garnick MB (2006) Abarelix for injectable suspension: first-in-class gonadotropin-releasing hormone antagonist for prostate cancer. Future Oncology 2:677–696

    Article  PubMed  CAS  Google Scholar 

  42. Kovacs M, Schally AV, Hohla F, Rick FG, Pozsgai E, Szalontay L et al (2010) A correlation of endocrine and anticancer effects of some antagonists of GHRH. Peptides 31:1839–1846

    Article  PubMed  CAS  Google Scholar 

  43. Sinnett-Smith J, Santiskulvong C, Duque J, Rozengurt E (2000) [D-Arg (1), D-Trp (5,7,9), Leu (11)]Substance P inhibits bombesin-induced mitogenic signal transduction mediated by both G(q) and G(12) in Swiss 3T3cells. J Biol Chem 275:30644–30652

    Article  PubMed  CAS  Google Scholar 

  44. Prasad S, Mathur A, Gupta N, Jaggi M, Singh AT, Rajendran P et al (2007) Bombesin analogs containing alpha-amino-isobutyric acid with potent anticancer activity. J Pept Sci (an official Publication of the European Peptide Society) 13:54–62

    CAS  Google Scholar 

  45. Jaggi M, Prasad S, Singh AT, Praveen R, Dutt S, Mathur A et al (2008) Anticancer activity of a peptide combination in gastrointestinal cancers targeting multiple neuropeptide receptors. Invest New Drugs 26:489–504

    Article  PubMed  CAS  Google Scholar 

  46. Paolillo M, Russo MA, Curti D, Lanni C, Schinelli S (2010) Endothelin B receptor antagonists block proliferation and induce apoptosis in glioma cells. Pharmacol Res (the official journal of Italian Pharmacological Society) 61:306–315

    Article  CAS  Google Scholar 

  47. Asgari S, Rivers DB (2011) Venom proteins from endoparasitoid wasps and their role in host-parasite interactions. Annu Rev Entomol 56:313–335

    Article  PubMed  CAS  Google Scholar 

  48. Gomes A, Bhattacharjee P, Mishra R, Biswas AK, Dasgupta SC, Giri B (2010) Anticancer potential of animal venoms and toxins. Indian J Exp Biol 48:93–103

    PubMed  CAS  Google Scholar 

  49. Markland FS, Shieh K, Zhou Q, Golubkov V, Sherwin RP, Richters V et al (2001) A novel snake venom disintegrin that inhibits human ovarian cancer dissemination and angiogenesis in an orthotopic nude mouse model. Haemostasis 31:183–191

    PubMed  CAS  Google Scholar 

  50. Gomes A, Choudhury SR, Saha A, Mishra R, Giri B, Biswas AK et al (2007) A heat stable protein toxin (drCT-I) from the Indian Viper (Daboia russelli russelli) venom having antiproliferative, cytotoxic and apoptotic activities. Toxicon (official journal of International Society on Toxinology) 49:46–56

    Article  CAS  Google Scholar 

  51. Das Gupta S, Debnath A, Saha A, Giri B, Tripathi G, Vedasiromoni JR et al (2007) Indian black scorpion (Heterometrus bengalensis Koch) venom induced antiproliferative and apoptogenic activity against human leukemic cell lines U937 and K562. Leuk Res 31:817–825

    Article  Google Scholar 

  52. Yang SH, Lu MC, Chien CM, Tsai CH, Lu YJ, Hour TC et al (2005) Induction of apoptosis in human leukemia K562 cells by cardiotoxin III. Life Sci 76:2513–2522

    Article  PubMed  CAS  Google Scholar 

  53. Tsai CH, Yang SH, Chien CM, Lu MC, Lo CS, Lin YH et al (2006) Mechanisms of cardiotoxin III-induced apoptosis in human colorectal cancer colo205 cells. Clin Exp Pharmacol Physiol 33:177–182

    Article  PubMed  CAS  Google Scholar 

  54. Chien CM, Yang SH, Yang CC, Chang LS, Lin SR (2008) Cardiotoxin III induces c-jun N-terminal kinase-dependent apoptosis in HL-60 human leukaemia cells. Cell Biochem Funct 26:111–118

    Article  PubMed  CAS  Google Scholar 

  55. Tsai PC, Hsieh CY, Chiu CC, Wang CK, Chang LS, Lin SR (2012) Cardiotoxin III suppresses MDA-MB-231 cell metastasis through the inhibition of EGF/EGFR-mediated signaling pathway. Toxicon (official journal of International Society on Toxinology) 60:734–743

    Article  CAS  Google Scholar 

  56. Chiu CC, Lin KL, Chien CM, Chang LS, Lin SR (2009) Effects of cardiotoxin III on NF-kappaB function, proliferation, and apoptosis in human breast MCF-7 cancer cells. Oncol Res 17:311–321

    Article  PubMed  Google Scholar 

  57. Fang EF, Ng TB (1815) Ribonucleases of different origins with a wide spectrum of medicinal applications. Biochim Biophys Acta 2011:65–74

    Google Scholar 

  58. Rozek T, Bowie JH, Wallace JC, Tyler MJ (2000) The antibiotic and anticancer active aurein peptides from the Australian Bell Frogs Litoria aurea and Litoria raniformis. Part 2. Sequence determination using electrospray mass spectrometry. Rapid Commun Mass Spectrom 14:2002–2011

    Article  PubMed  CAS  Google Scholar 

  59. Rozek T, Wegener KL, Bowie JH, Olver IN, Carver JA, Wallace JC et al (2000) The antibiotic and anticancer active aurein peptides from the Australian Bell Frogs Litoria aurea and Litoria raniformis the solution structure of aurein 1.2. Eur J Biochem/FEBS 267:5330–5341

    Article  CAS  Google Scholar 

  60. Cho JH, Sung BH, Kim SC (2009) Buforins: histone H2A-derived antimicrobial peptides from toad stomach. Biochim Biophys Acta 1788:1564–1569

    Article  PubMed  CAS  Google Scholar 

  61. Liberio MS, Joanitti GA, Azevedo RB, Cilli EM, Zanotta LC, Nascimento AC et al (2011) Anti-proliferative and cytotoxic activity of pentadactylin isolated from Leptodactylus labyrinthicus on melanoma cells. Amino Acids 40:51–59

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The award of research grants (Research Funds for the Control of Infectious Diseases project number 10090812, 12110672, and 12110282) from Food and Health Bureau, Government of Hong Kong, is gratefully acknowledged.

Author information

Authors and Affiliations

  1. School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong

    Tzi Bun Ng, Evandro Fei Fang & Jack Ho Wong

  2. Laboratory of Molecular Gerontology, National Institute on Aging National Institutes of Health, Baltimore, MD, 21224, USA

    Evandro Fei Fang

Authors
  1. Tzi Bun Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Evandro Fei Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jack Ho Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tzi Bun Ng .

Editor information

Editors and Affiliations

  1. , Laboratory of Molecular Gerontology, National Institute on Aging, NIH, Bayview Boulevard Street 251, Baltimore, 21224-6825, Maryland, USA

    Evandro Fei Fang

  2. , School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, Hong Kong SAR

    Tzi Bun Ng

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Ng, T.B., Fang, E.F., Wong, J.H. (2013). Proteins with Anticancer and Antimicrobial Activities from Mammals, Submammalian Vertebrates and Invertebrates. In: Fang, E., Ng, T. (eds) Antitumor Potential and other Emerging Medicinal Properties of Natural Compounds. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6214-5_23

Download citation

Publish with us

Policies and ethics

Search

Navigation