Skip to main content

Advertisement

Log in

The role of nutraceutical proteins and peptides in apoptosis, angiogenesis, and metastasis of cancer cells

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

The process of carcinogenesis is complex and not easy to eliminate. It includes the initial occurrence of genetic alterations which can lead to the inactivation of tumor-suppressor genes and further accumulation of genetic alterations during tumor progression. Looking for food and food components with biological properties, collectively called nutraceuticals, that can hinder such alterations and prevent the inactivation of tumor-suppressor genes is a very promising area for cancer prevention. Proteins and peptides are one group of nutraceuticals that show potential results in preventing the different stages of cancer including initiation, promotion, and progression. In this review, we summarized current knowledge on the use of nutraceutical proteins and peptides in cancer prevention and treatment. We focused on the role of plant protease inhibitors, lactoferrin and lactoferricin, shark cartilage, plant lectins, and lunasin in the apoptosis, angiogenesis, and metastasis of cancer cells. Also included are studies on bioavailability and clinical trials conducted on these promising proteins and peptides.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Zaloga, G. P., & Siddiqui, R. A. (2004). Biologically active dietary peptides. Mini-Reviews in Medicinal Chemistry, 4, 815–821.

    CAS  PubMed  Google Scholar 

  2. Haller, C. A. (2010). Nutraceuticals: has there been any progress? Clinical Pharmacology and Therapeutics, 87, 137–141.

    Article  CAS  PubMed  Google Scholar 

  3. Lakra, E. K. (2003). Nutraceutical—definition and introduction. AAPS PharmSci, 5, 1–2.

    Google Scholar 

  4. Grimble, G. K. (1994). The significance of peptides in clinical nutrition. Annual Review of Nutrition, 14, 419–447.

    Article  CAS  PubMed  Google Scholar 

  5. Jemal, A., Siegel, R., Ward, E., Hao, Y. P., Xu, J. Q., & Thun, M. J. (2009). Cancer statistics, 2009. CA: A Cancer Journal for Clinicians, 59, 225–249.

    Article  Google Scholar 

  6. Greene, F. L., Stewart, A. K., & Norton, H. J. (2002). A new TNM staging strategy for node-positive (stage III) colon cancer: an analysis of 50,042 patients. Annals of Surgery, 236, 416–421.

    Article  PubMed  Google Scholar 

  7. O’Connell, J. B., Maggard, M. A., & Ko, C. Y. (2004). Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. Journal of the National Cancer Institute, 96, 1420–1425.

    Article  PubMed  Google Scholar 

  8. Meyerhardt, J. A., & Mayer, R. J. (2005). Systemic therapy for colorectal cancer. The New England Journal of Medicine, 352, 476–487.

    Article  CAS  PubMed  Google Scholar 

  9. West, N. J., Courtney, E. D. J., Poullis, A. P., & Leicester, R. J. (2009). Apoptosis in the colonic crypt, colorectal adenomata and manipulation by chemoprevention. Cancer Epidemiology, Biomarkers & Prevention, 18, 1680–1687.

    Article  CAS  Google Scholar 

  10. Wyllie, A. H., Beattie, G. J., & Hargreaves, A. D. (1981). Chromatin changes in apoptosis. The Histochemical Journal, 13, 681–692.

    Article  CAS  PubMed  Google Scholar 

  11. Wyllie, A. H. (1980). Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature, 284, 555–556.

    Article  CAS  PubMed  Google Scholar 

  12. Okada, H., & Mak, T. W. (2004). Pathways of apoptotic and non-apoptotic death in tumor cells. Nature Reviews. Cancer, 4, 592–603.

    Article  CAS  PubMed  Google Scholar 

  13. Debatin, K. M., & Krammer, P. H. (2004). Death receptors in chemotherapy and cancer. Oncogene, 23, 2950–2966.

    Article  CAS  PubMed  Google Scholar 

  14. Hanahan, D., & Weeinberg, R. A. (2000). The hallmarks of cancer. Cell, 100, 57–70.

    Article  CAS  PubMed  Google Scholar 

  15. Murukesh, N., Dive, C., & Jayson, G. C. (2010). Biomarkers of angiogenesis and their roles in the development of VEGF inhibitors. British Journal of Cancer, 102, 8–18.

    Article  CAS  PubMed  Google Scholar 

  16. Boehm, S., Rothermundt, C., Hess, D., & Joerger, M. (2010). Antiangiogenic drugs in oncology: a focus on drug safety and the elderly—a mini-review. Gerontology, 56, 303–309.

    Article  CAS  PubMed  Google Scholar 

  17. Winder, T., & Lenz, H. J. (2010). Vascular endothelial growth factor and epidermal growth factor signaling pathways as therapeutic targets for colorectal cancer. Gastroenterology, 138, 2163–2176.

    Article  CAS  PubMed  Google Scholar 

  18. Korpanty, G., Smyth, E., Sullivan, L. A., Brekken, R. A., & Carney, D. (2010). Antiangiogenic therapy in lung cancer: focus on vascular endothelial growth factor pathway. Experimental Biology and Medicine, 235, 3–9.

    Article  CAS  PubMed  Google Scholar 

  19. Tan, A. H., Xia, N., Gao, F., Mo, Z. N., & Cao, Y. F. (2010). Angiogenesis-inhibitors for metastatic thyroid cancer. Cochrane Database of Systematic Reviews, 3, CD007958.

    Google Scholar 

  20. Westermarck, J., & Kahari, V. M. (1999). Regulation of matrix metalloproteinase expression in tumor invasion. The FASEB Journal, 13, 781–792.

    CAS  PubMed  Google Scholar 

  21. Losso, J. N. (2008). The biochemical and functional food properties of the Bowman–Birk inhibitor. Critical Reviews in Food Science and Nutrition, 48, 94–118.

    Article  CAS  PubMed  Google Scholar 

  22. Clemente, A., & Domoney, C. (2006). Biological significance of polymorphism in legume protease inhibitors from the Bowman–Birk family. Current Protein & Peptide Science, 7, 201–216.

    Article  CAS  Google Scholar 

  23. Meykens, F. L. (2001). Development of Bowman–Birk inhibitor for chemoprevention of oral head and neck cancer. Cancer prevention—molecular mechanisms to clinical applications. Annals of the New York Academy of Sciences, 952, 116–123.

    Article  Google Scholar 

  24. Saito, T., Sato, H., Virgona, N., Hagiwara, H., Kashiwagi, K., Suzuki, K., et al. (2007). Negative growth control of osteosarcoma cell by Bowman–Birk protease inhibitor from soybean; involvement of connexin 43. Cancer Letters, 253, 249–257.

    Article  CAS  PubMed  Google Scholar 

  25. Suzuki, K., Yano, T., Sadzuka, Y., Sugiyama, T., Seki, T., & Asano, R. (2005). Restoration of connexin 43 by Bowman–Birk protease inhibitor in M5076 bearing mice. Oncology Reports, 13, 1247–1250.

    CAS  PubMed  Google Scholar 

  26. Chen, Y. W., Huang, S. C., Lin-Shiau, S. Y., & Lin, J. K. (2005). Bowman–Birk inhibitor abates proteasome function and suppresses the proliferation of MCF7 breast cancer cells through accumulation of MAP kinase phosphatase-1. Carcinogenesis, 26, 1296–1306.

    Article  CAS  PubMed  Google Scholar 

  27. Du, X., Beloussow, K., & Shei, W. C. (2001). Bowman–Birk protease inhibitor and its palmitic acid conjugate prevent 7,12-dimethylbenz[a]anthracene-induced transformation in cultured mouse mammary glands. Cancer Letters, 164, 135–141.

    Article  CAS  PubMed  Google Scholar 

  28. Honeycutt, L., Wang, J., Whrami, H., & Shen, W. C. (1996). Comparison of pharmacokinetic parameters of a polypeptide, the Bowman–Birk protease inhibitor (BBI) and its palmitic acid conjugate. Pharmaceutical Research, 13, 1373–1377.

    Article  CAS  PubMed  Google Scholar 

  29. Joanitti, G. A., Azevedo, R. B., & Freitas, S. M. (2010). Apoptosis and lysosome membrane permeabilization induction on breast cancer cells by an anticarcinogenic Bowman–Birk protease inhibitor from Vigna unguiculata seeds. Cancer Letters, 293, 73–81.

    Article  CAS  PubMed  Google Scholar 

  30. Kennedy, A. R., & Wan, X. S. (2002). Effects of the Bowman–Birk inhibitor on growth, invasion, and clonogenic survival of human prostate epithelial cells and prostate cancer cells. The Prostate, 50, 125–133.

    Article  CAS  PubMed  Google Scholar 

  31. Tang, M. X., Asamoto, M., Ogawa, K., Naiki-Ito, A., Sato, S., Takahashi, S., et al. (2009). Induction of apoptosis in the LNCap human prostate carcinoma cell line and prostate adenocarcinomas of SV40T antigen transgenic rats by the Bowman–Birk inhibitor. Pathology International, 59, 790–796.

    Article  CAS  PubMed  Google Scholar 

  32. Kennedy, A. R., Billings, P. C., Wan, X. S., & Newberne, P. M. (2002). Effects of Bowman–Birk inhibitor on rat colon carcinogenesis. Nutrition and Cancer, 43, 174–186.

    Article  CAS  PubMed  Google Scholar 

  33. Caccialupi, P., Ceci, L. R., Siciliano, R. A., Pignone, D., Clemente, A., & Sonnante, G. (2010). Bowman–Birk inhibitors in lentil: heterologous expression, functional characterization and anti-proliferative properties in human colon cancer cells. Food Chemistry, 120, 1058–1066.

    Article  CAS  Google Scholar 

  34. Clemente, A., Gee, J. M., Johnson, I. T., MacKenzie, D. A., & Domoney, C. (2005). Pea (Pisum sativum L.) protease inhibitors from the Bowman–Birk class influence the growth of human colorectal adenocarcinoma HT29 cells in vitro. Journal of Agricultural and Food Chemistry, 53, 8979–8986.

    Article  CAS  PubMed  Google Scholar 

  35. Clemente, A., Moreno, F. J., Marin-Manzano, M. C. D., Jimenez, E., & Domoney, C. (2010). The cytotoxic effect of Bowman–Birk isoinhibitors, IBB1 and IBBD2, from soybean (Glycine max) on HT29 human colorectal cancer cells is related to their intrinsic ability to inhibit serine proteases. Molecular Nutrition & Food Research, 54, 396–405.

    Article  CAS  Google Scholar 

  36. Armstrong, W. B., Wan, X. S., Kennedy, A. R., Taylor, T. H., & Meyskens, F. L. (2003). Development of the Bowmn-Birk inhibitor for oral cancer chemoprevention and analysis of neu immunohistochemical staining intensity with Bowman–Birk inhibitor concentrate treatment. The Laryngoscope, 113, 1687–1702.

    Article  CAS  PubMed  Google Scholar 

  37. Armstrong, W. B., Kennedy, A. R., Wan, X. S., Taylor, T. H., Nguyen, Q. A., Jensen, J., et al. (2000). Clinical modulation of oral leukoplakia and protease activity by Bowman–Birk inhibitor concentrate in a Phase IIa chemoprevention trial. Clinical Cancer Research, 6, 4684–4691.

    CAS  PubMed  Google Scholar 

  38. Kennedy, A. R., Kritchevsky, D., & Shen, W. C. (2003). Effects of spermine-conjugated Bowman–Birk inhibitor (spermine-BBI) on carcinogenesis and cholesterol biosynthesis in mice. Pharmaceutical Research, 20, 1908–1910.

    Article  CAS  PubMed  Google Scholar 

  39. Witschi, H., & Espiritu, I. (2002). Development of tobacco-smoke-induced lung tumors in mice fed Bowman–Birk protease inhibitor concentrate. Cancer Letters, 183, 141–146.

    Article  CAS  PubMed  Google Scholar 

  40. Kobayashi, H., Fukuda, Y., Yoshida, R., Kanada, Y., Nishiyama, S., & Suzuki, M. (2004). Suppressing effects of dietary supplementation of soybean trypsin inhibitor on spontaneous, experimental and peritoneal disseminated metastasis in mouse model. International Journal of Cancer, 112, 519–524.

    Article  CAS  Google Scholar 

  41. Kunitz, M. (1945). Cystallization of a trypsin inhibitor from soybean. Science, 101, 668–669.

    Article  CAS  PubMed  Google Scholar 

  42. Kobayashi, H., Suzuki, M., Kanayama, N., & Terao, T. (2004). A soybean Kunitz trypsin inhibitor suppresses ovarian cancer cell invasion by blocking urokinase upregulation. Clinical & Experimental Metastasis, 21, 159–166.

    Article  CAS  Google Scholar 

  43. Inagaki, K., Kobayashi, H., Yoshida, R., Kanada, Y., Fukuda, Y., Yagyu, T., et al. (2005). Suppression of urokinase expression and invasion by a soybean Kunitz trypsin inhibitor are mediated through inhibition of Src-dependent signaling pathways. The Journal of Biological Chemistry, 280, 31428–31437.

    Article  CAS  PubMed  Google Scholar 

  44. Fang, E. F., Wong, J. H., & Ng, T. B. (2010). Thermostable Kunitz trypsin inhibitor with cytokine inducing, antitumor and HIV-1 reverse transcriptase activities from Korean large black soybeans. Journal of Bioscience and Bioengineering, 109, 211–217.

    Article  CAS  PubMed  Google Scholar 

  45. Park, S. S., & Ohba, H. (2004). Suppressive activity of protease inhibitors from buckwheat seeds against human T-acute lymphoblastic leukemia cell lines. Applied Biochemistry and Biotechnology, 117, 65–74.

    Article  CAS  PubMed  Google Scholar 

  46. Zhang, Z., Li, Y., Li, C., Yuan, J., & Wang, Z. (2007). Expression of a buckwheat trypsin inhibitor gene in Escherichia coli and its effect on multiple myeloma IM-9 cell proliferation. Acta Biochimica et Biophysica Sinica, 39, 701–707.

    Article  CAS  PubMed  Google Scholar 

  47. Wang, Z. H., Gao, L., Li, Y. Y., Zhang, Z., Yuan, J. M., Wang, H. W., et al. (2007). Induction of apoptosis by buckwheat trypsin inhibitor in chronic myeloid leukemia K562 cells. Biological & Pharmaceutical Bulletin, 30, 783–786.

    Article  CAS  Google Scholar 

  48. Li, Y. Y., Zhang, Z., Wang, Z. H., Wang, H. W., Zhang, L., & Zhu, L. (2009). rBTI induces apoptosis in human solid tumor cell lines by loss in mitochondrial transmembrane potential and caspase activation. Toxicology Letters, 189, 166–175.

    Article  CAS  PubMed  Google Scholar 

  49. Troncoso, M. F., Zolezzi, P. C., Hellman, U., & Wolfenstein-Todel, C. (2003). A novel trypsin inhibitor from Peltophorum dubium seeds, with lectin-like properties, triggers rat lymphoma apoptosis. Archives of Biochemistry and Biophysics, 411, 93–104.

    Article  Google Scholar 

  50. Huang, G. H., Sheu, M. J., Chen, H. J., Chang, Y. S., & Lin, Y. H. (2007). Growth inhibition and induction of apoptosis in NB4 promyelocytic leukemia cells by trypsin inhibitor from sweet potato storage roots. Journal of Agricultural and Food Chemistry, 55, 2548–2553.

    Article  CAS  PubMed  Google Scholar 

  51. Severe, N., Filipic, M., Brzin, J., & Lah, T. T. (2002). Effect of cysteine proteinase inhibitors on murine B16 melanoma cell invasion in vitro. Biological Chemistry, 383, 839–842.

    Article  Google Scholar 

  52. Blanco-Aparicio, C., Molina, M. A., Fernandez-Salas, E., Frazier, M. L., Mas, J. M., Querol, E., et al. (1998). Potato carboxypeptidase inhibitor, a T-knot protein, is an epidermal growth factor antagonist that inhibits tumor cell growth. The Journal of Biological Chemistry, 273, 12370–12377.

    Article  CAS  PubMed  Google Scholar 

  53. Sitja-Arnau, M., Molina, M. A., Blano-Aparicio, C., Ferrer-Soler, L., Lorenzo, J., Aviles, F. X., et al. (2005). Mechanism of action of potato carboxypeptidase inhibitor (PCI) as an EGF blocker. Cancer Letters, 226, 169–184.

    Article  CAS  PubMed  Google Scholar 

  54. Ashida, K., Sazaki, H., Suzuki, Y. A., & Lonnerdal, B. (2004). Cellular internalization of lactoferrin in intestinal epithelial cells. Biometals, 17, 311–315.

    Article  CAS  PubMed  Google Scholar 

  55. Suzuki, Y. A., Lopez, B., & Lonnerdal, B. (2005). Mammalian lactoferrin receptors: structure and function. Cellular and Molecular Life Sciences, 62, 2560–2575.

    Article  CAS  PubMed  Google Scholar 

  56. Son, K. A., Park, J., Chung, C. K., Chung, D. K., Yu, D. Y., Lee, K. K., et al. (2002). Human lactoferrin activates transcription of IL-1 beta gene in mammalian cells. Biochemical and Biophysical Research Communications, 290, 236–241.

    Article  CAS  PubMed  Google Scholar 

  57. Lonneral, B. (2009). Nutritional roles of lactoferrin. Current Opinion in Clinical Nutrition and Metabolic Care, 12, 293–297.

    Article  CAS  Google Scholar 

  58. Actor, J. K., Hwang, S. A., & Kruzel, M. L. (2009). Lactoferrin as a natural immune modulator. Current Pharmaceutical Design, 15, 1956–1973.

    Article  CAS  PubMed  Google Scholar 

  59. Gonzalez-Chavez, S. A., Arevalo-Gallegos, S., & Rascon-Cruz, Q. (2009). Lactoferrin: structure, function and applications. International Journal of Antimicrobial Agents, 33, 301–306.

    Article  PubMed  CAS  Google Scholar 

  60. Lonnerdal, B., & Iyer, S. (1995). Lactoferrin—molecular structure and biological function. Annual Review of Nutrition, 15, 93–110.

    Article  CAS  PubMed  Google Scholar 

  61. Rodirgues, L., Teixera, J., Fernando, S., Paulsson, M., & Mansson, H. L. (2009). Lactoferin and cancer disease prevention. Critical Reviews in Food Science and Nutrition, 49, 203–217.

    Article  CAS  Google Scholar 

  62. Damiens, E., Yazidi, I. E., Mazurier, J., Duthille, I., Spik, G., & Boily-Marer, Y. (1999). Lactoferrin inhibits G1 cyclin-dependent kinases during growth arrest of human breast carcinoma cells. Journal of Cellular Biochemistry, 74, 486–498.

    Article  CAS  PubMed  Google Scholar 

  63. Xiao, Y., Monitto, C. L., Minhas, K. M., & Sidransky, D. (2004). Lactoferrin down-regulates G1 cyclin-dependent kinases during growth arrest of head and neck cancer cells. Clinical Cancer Research, 10, 8683–8686.

    Article  CAS  PubMed  Google Scholar 

  64. Son, H. J., Lee, S. H., & Choi, S. Y. (2006). Human lactoferrin controls the level of retinoblastoma protein and its activity. Biochemistry and Cell Biology, 84, 345–350.

    Article  CAS  PubMed  Google Scholar 

  65. Wolf, J. S., Li, G., Varadhachary, A., Petark, K., Schneyer, M., Li, D., et al. (2007). Oral lactoferrin results in T cell-dependent tumor inhibition of head and neck squamous cell carcinoma in vivo. Clinical Cancer Research, 13, 1601–1610.

    Article  CAS  PubMed  Google Scholar 

  66. Mohan, K. V. P. C., Kumaragupuran, R., Prathiba, D., & Nagini, S. (2006). Modulation of xenobiotic-metabolizing enzymes and redox status during chemoprevention of hamster buccal carcinogenesis by bovine lactoferrin. Nutrition, 22, 940–946.

    Article  CAS  Google Scholar 

  67. Matsuda, Y., Saoo, K., Hosokawa, K., Yamakawa, K., Yokohira, M., Zeng, Y., et al. (2007). Post-initiation chemopreventive effects of dietary bovine lactoferrin on 4-(methynitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in female A/J mice. Cancer Letters, 246, 41–46.

    Article  CAS  PubMed  Google Scholar 

  68. Zemann, N., Klein, P., Wetzel, E., Huettinger, F., & Huettinger, M. (2010). Lactoferrin induces growth arrest and nuclear accumulation of Smad-2 in Hela cells. Biochimie, 92, 880–884.

    Article  CAS  PubMed  Google Scholar 

  69. Norrby, K., Mattsby-Baltzer, I., Innocenti, M., & Tuneberg, S. (2001). Orally administered bovine lactoferrin systemically inhibits VEGF165-mediated angiogenesis in the rat. International Journal of Cancer, 91, 236–240.

    Article  CAS  Google Scholar 

  70. Shimamura, M., Yamamoto, Y., Ashino, H., Oikawa, T., Hazato, T., Tsuda, H., et al. (2004). Bovine lactoferrin inhibits tumor-induced angiogenesis. International Journal of Cancer, 111, 111–116.

    Article  CAS  Google Scholar 

  71. Tsuda, K., Sekine, K., Takasuka, N., Toriyama-Baba, H., & Iigo, M. (2000). Prevention of colon carcinogenesis and carcinoma metastasis by orally administered bovine lactoferrin in animals. Biofactors, 12, 83–88.

    Article  CAS  PubMed  Google Scholar 

  72. Kuhara, T., Iigo, M., Itoh, T., Ushida, Y., Sekine, K., Terada, N., et al. (2000). Orally administered lactoferrin exerts an antimetastatic effect and enhances production of IL-18 in the intestinal epithelium. Nutrition and Cancer, 38, 192–199.

    Article  CAS  PubMed  Google Scholar 

  73. Iigo, M., Shimamura, M., Matsuda, E., Fujita, K., Nomoto, H., Satoh, J., et al. (2004). Orally administered bovine lactoferrin induces casapse-1 and interleukin-18 in the mouse intestinal mucosa: a possible explanation for inhibition of carcinogenesis and metastasis. Cytokine, 25, 36–44.

    Article  CAS  PubMed  Google Scholar 

  74. Sakamoto, K., Ito, Y., Mori, T., & Sugimura, K. (2006). Interaction of human lactoferrin with cell adhesion molecules through RGD motif elucidated by lactoferrin-binding epitopes. The Journal of Biological Chemistry, 281, 24472–24478.

    Article  CAS  PubMed  Google Scholar 

  75. McKeown, S. T. W., Lundy, F. T., Nelson, J., Lockhart, D., Irwin, C. R., Cowan, C. G., et al. (2006). The cytotoxic effects of human neutrophil peptides-1 (HNP1) and lactoferrin on oral squamous cell carcinoma (OSCC) in vitro. Oral Oncology, 42, 685–690.

    Article  CAS  PubMed  Google Scholar 

  76. Mohan, K. V., 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 Biology International, 31, 599–608.

    Article  CAS  PubMed  Google Scholar 

  77. Letchoumy, P. V., Mohan, K. V., Stegeman, J. J., Gelboin, H. V., Hara, Y., & Nagini, S. (2008). In vitro antioxidative potential of lactoferrin and black tea polyphenols and protective effects in vivo on carcinogen activation, DNA damage, proliferation, invasion, and angiogenesis during experimental oral carcinogenesis. Oncology Research, 2008(17), 193–203.

    Article  Google Scholar 

  78. Mohan, K. V. P. C., Letchoumy, P. V., Hara, Y., & Nagini, S. (2008). Combination chemoprevention of hamster buccal pouch carcinogenesis by bovine milk lactoferrin and black tea polyphenols. Cancer Investigation, 26, 193–201.

    Article  CAS  PubMed  Google Scholar 

  79. Haba, R., Watanabe, S., Masahiro, W., & Udaka, S. (2004). Effects of lactoferrin, soya germ and polyamine on 2-amino-1methyl-6-phenylimidazo[4,5-b]-pyridine(PhIP)-induced breast carcinogenesis in rats. Biofactors, 22, 127–131.

    Article  CAS  PubMed  Google Scholar 

  80. Ward, P. P., Paz, E., & Conneely, O. M. (2005). Multifunctional roles of lactoferrin: a critical overview. Cellular and Molecular Life Sciences, 22, 2540–2548.

    Article  CAS  Google Scholar 

  81. McBride, D. (2007). Talactoferrin alpha receives fast-track designation for the treatment of non-small cell lung cancer. ONS Connect, 22, 14.

    PubMed  Google Scholar 

  82. Wang, Y., Raghunadharao, D., Raman, G., Doval, D., Advani, S., Julka, P., et al. (2006). Adding oral talactoferrin to first-line NSCLC chemotherapy safely enhanced efficacy in a randomized trial. Journal of Clinical Oncology, 24, 187.

    Google Scholar 

  83. Hayes, T. G., Faclchook, G. F., Varadhachary, G. R., Smith, D. P., Davis, L. D., Dhingra, H. M., et al. (2006). Phase I trial of oral talactoferrin alfa in refractory solid tumors. Investigational New Drugs, 24, 233–240.

    Article  CAS  PubMed  Google Scholar 

  84. Hayes, T. G., Falchook, G. S., & Varadhachary, A. (2010). Phase IB trial of oral talactoferrin in the treatment of patients with metastatic solid tumors. Investigational New Drugs, 28, 156–162.

    Article  CAS  PubMed  Google Scholar 

  85. Jonasch, E., Stadler, W. M., Bukowski, R. M., Hayes, T. G., 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  CAS  PubMed  Google Scholar 

  86. Bellamy, w, Takase, M., Wakabayashi, H., Kawase, K., & Tomita, M. (1992). Antibacterial spectrum of lactoferricin-B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin. The Journal of Applied Bacteriology, 73, 472–479.

    CAS  PubMed  Google Scholar 

  87. Sakai, T., Banno, Y., Kato, Y., Nozawa, Y., & Kawaguchi, M. (2005). Pepsin-digested lactoferrin induces apoptotic cell death with JNK/SAPK activation in oral cancer cells. Journal of Pharmacological Sciences, 98, 41–48.

    Article  CAS  PubMed  Google Scholar 

  88. Mader, S. J., Salsman, J., Conrad, D. M., & Hoskin, D. W. (2005). Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cell lines. Molecular Cancer Therapeutics, 4, 612–624.

    Article  CAS  PubMed  Google Scholar 

  89. Eliassen, L. T., Berge, G., Leknessund, A., Wikman, M., Lindin, I., Lokke, C., et al. (2006). The antimicrobial peptide, Lactoferricin B, is cytotoxic to neuroblastoma cells in vitro and inhibits xenograft growth in vivo. International Journal of Cancer, 119, 493–500.

    Article  CAS  Google Scholar 

  90. Freiburgahus, C., Janicke, B., Lindmark-Mansson, H., Oredsson, S. M., & Paulsson, M. A. (2009). Lactoferricin treatment decreases the rate of cell proliferation of a human colon cancer cell line. Journal of Dairy Science, 92, 247–2484.

    Article  CAS  Google Scholar 

  91. Richardosn, A., de Antueno, R., Duncan, R., & Hoskin, D. W. (2009). Intracellular delivery of bovine lactoferricin’s antimicrobial core (RRWQWR) kills T-leukemia cells. Biochemical and Biophysical Research Communications, 388, 736–741.

    Article  CAS  Google Scholar 

  92. Berge, G., Eliassen, L. T., Camilio, K. A., Bartnes, K., Sveinbjornsson, B., & Rekdal, O. (2010). Therapeutic vaccination against a murine lymphoma by intratumoral injection of a cationic anticancer peptide. Cancer Immunology, Immunotherapy, 59, 1285–1294. doi:10.1007/s00262-010-0857-6.

    Article  CAS  PubMed  Google Scholar 

  93. Yoo, Y. C., Watanabe, S., Wataanbe, R., Hata, K., Shimazaki, K., & Azuma, I. (1997). Bovine lactoferrin and lactoferricin, a peptide derived from bovine lactoferrin, inhibit tumor metastasis in mice. Japanese Journal of Cancer, 88, 184–190.

    CAS  Google Scholar 

  94. Mader, S., Smyth, D., Marshall, J., & Hoskin, D. W. (2006). Bovine lactoferricin inhibits basic fibroblast growth factor- and vascular endothelial growth factor165-induced angiogenesis by competing for heparin-like binding sites on endothelial cells. The American Journal of Pathology, 169, 1753–1766.

    Article  CAS  PubMed  Google Scholar 

  95. Dupont, E., Falardeu, P., Mousa, S. A., Dimitriadou, V., Pepin, M. C., Wang, T., et al. (2002). Antiangiogenic and antimetastatic properties of Neovastat (AE-941), an orally active extract derived from cartilage tissue. Clinical & Experimental Metastasis, 19, 145–153.

    Article  CAS  Google Scholar 

  96. Sheu, J. R., Fu, C. C., tsai, M. L., & Chung, W. J. (1998). Effect of U-995, a potent shark cartilage-derived angiogenesis inhibitor, on anti-angiogenesis and anti-tumor activities. Anticancer Research, 18, 4435–4441.

    CAS  PubMed  Google Scholar 

  97. Feyzi, R., Hassan, Z. M., & Mostafaie, A. (2003). Modulation of CD +4 and CD +8 tumor infiltrating lymphocytes by a fractions isolated from shark cartilage: shark cartilage modulates anti-tumor immunity. International Immunopharmacology, 3, 921–926.

    Article  CAS  PubMed  Google Scholar 

  98. Hassan, Z. M., Feyzi, R., Sheikhian, A., Bargahi, A., Mostafaie, A., Mansouri, K., et al. (2005). Low molecular weight fraction of shark cartilage can modulate immune responses and abolish angiogenesis. International Immunopharmacology, 5, 961–970.

    Article  CAS  PubMed  Google Scholar 

  99. Chen, J. S., Chang, C. M., Wu, J. C., & Wang, S. M. (2000). Shark cartilage extract interferes with cell adhesion and induces reorganization of focal adhesions in cultured endothelial cells. Journal of Cellular Biochemistry, 78, 417–428.

    Article  CAS  PubMed  Google Scholar 

  100. Zeng, F., Xie, T. X., Yang, W. X., Zhang, Z. X., yu, J. X., & Pang, Y. (2001). A preliminary study of purification and bioactivity of a 12,000 shark cartilage angiogenesis inhibitor. Chemical Journal of Chinese Universities, 2, 1462–1465.

    Google Scholar 

  101. Shen, X. R., Ji, D. M., hu, Y. Q., jia, F. X., Wang, L., Chu, Z. Y., et al. (2001). SCAIF80, a novel inhibitor of angiogenesis, and its effect on tumor growth. Acta Biochimica et Biophysica Sinica, 33, 99–104.

    CAS  PubMed  Google Scholar 

  102. Zeng, F., Yang, W. X., Cui, K. Y., Liu, W., Zhang, Z. X., Yu, J. X., et al. (2003). Studies on purification and bioactivity of 17,400 shark cartilage angiogenesis inhibitor. Chemical Journal of Chinese Universities, 24, 1588–1591.

    CAS  Google Scholar 

  103. Luo, H., Xu, J., & yu, X. (2007). Isolation and bioactivity of an angiogenesis inhibitor extracted from the cartilage of Dasyatis akajei. Asia Pacific Journal of Clinical Nutrition, 16, 286–289.

    CAS  PubMed  Google Scholar 

  104. Kern, B. E., Balcom, J. H., Antoniu, B. A., Warshaw, A. L., & Fernandez-del Castillo, C. (2003). Troponin I peptide (Glu94-Leu123), a cartilage-derived angiogenesis inhibitor: in vitro and in vivo effects on human endothelial cells and pancreatic cancer. Journal of Gastrointestinal Surgery, 7, 961–969.

    Article  PubMed  Google Scholar 

  105. Bukowski, R. M. (2003). AE-941, a multifunctional antiangiogenic compound: trials in renal cell carcinoma. Expert Opinion on Investigational Drugs, 12, 1403–1411.

    Article  CAS  PubMed  Google Scholar 

  106. Barber, R., Delahun, B., Grebe, S. K. G., Davis, P. F., Thornton, A., & Slim, G. C. (2001). Oral shark cartilage does not abolish carcinogenesis but delays tumor progression in a murine model. Anticancer Research, 21, 1065–1069.

    CAS  PubMed  Google Scholar 

  107. Horsman, M. R., Alsner, J., & Overgaard, J. (1998). The effect of shark cartilage extracts on the growth and metastatic spread of the SCCVII carcinoma. Acta Oncologica, 37, 441–445.

    Article  CAS  PubMed  Google Scholar 

  108. Miller, D. R., Anderson, G. T., Stark, J. J., Granick, J. L., & Richardson, D. (1998). Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. Journal of Clinical Oncology, 16, 3649–3655.

    CAS  PubMed  Google Scholar 

  109. Loprinzi, C. L., Levitt, R., Barton, B. L., Sloan, J. A., Atherton, P. J., Smith, D. J., et al. (2005). Evaluation of shark cartilage in patients with advanced cancer: a North Central Cancer Treatment Group Trial. Cancer, 104, 176–182.

    Article  PubMed  Google Scholar 

  110. Zheng, L., Ling, P., Wang, Z., Niu, R., Hu, C., Zhang, T., et al. (2007). A novel polypeptide from shark cartilage with potent anti-angiogenic activity. Cancer Biology & Therapy, 6, 775–780.

    Article  CAS  Google Scholar 

  111. Abbani-Chadegani, A., Abdossamadi, S., Bargahi, A., & Yousef-Masboogh, M. (2008). Identification of low-molecular weight protein (SCP1) from shark cartilage with anti-angiogenesis activity and sequence similarity to parvalbumin. Journal of Pharmaceutical and Biomedical Analysis, 46, 563–567.

    Article  CAS  Google Scholar 

  112. Murota, I., Tamai, T., Baba, T., Sato, R., Hashimoto, K., Park, E. Y., et al. (2010). Uric acid lowering effect by ingestion of proteolytic digest of shark cartilage and its basic fraction. Journal of Food Biochemistry, 34, 182–194.

    Article  CAS  Google Scholar 

  113. Sharon, N. (2008). Lectins: past, present, and future. Biochemical Society Transactions, 36, 1457–1460.

    Article  CAS  PubMed  Google Scholar 

  114. Van Damme, E. J. M., Peumans, W. J., Barre, A., & Rouge, P. (1998). Plant lectins: a composite of several distinct families of structurally related and evolutionary related proteins with diverse biological roles. Critical Reviews in Plant Sciences, 17, 575–692.

    Google Scholar 

  115. Liu, B., Bian, H., & Bao, J. (2010). Plant lectins: potential antineoplastic drugs from bench to clinic. Cancer Letters, 287, 1–12.

    Article  CAS  PubMed  Google Scholar 

  116. de Mejia, E. G., & Prisecaru, V. I. (2005). Lectins as bioactive plant proteins: a potential in cancer treatment. Critical Reviews in Food Science and Nutrition, 45, 425–445.

    Article  PubMed  CAS  Google Scholar 

  117. Pryme, I. F., Bardocz, S., Pusztail, A., & Ewen, S. W. B. (2006). Suppression of growth of tumour cell lines in vitro and tumours in vivo by mistletoe lectins. Histology and Histopathology, 21, 285–299.

    CAS  PubMed  Google Scholar 

  118. Lin, P., & Ng, T. B. (2008). Preparation and biological properties of a melibiose binding lectin from Bauhinia variegate seeds. Journal of Agricultural and Food Chemistry, 56, 10481–10486.

    Article  CAS  PubMed  Google Scholar 

  119. Sharma, A., Ng, T. B., Wong, J. H., & Lin, P. (2009). Purification and characterization of a lectin from Phaseolus vulgaris cv. (Anasazi beans). Journal of Biomedicine & Biotechnology, 2009, 929568.

    Google Scholar 

  120. Chen, J., Liu, B., Ji, N., Zhou, J., Bian, H., Li, C., et al. (2009). A novel sialic acid-specific lectin from Phaseolus coccineus seeds with potent antineoplastic and antifungal activities. Phytomedicine, 16, 352–360.

    Article  CAS  PubMed  Google Scholar 

  121. Liu, B., Min, M., & Bao, J. K. (2009). Induction of apoptosis by concanavalin A and its molecular mechanisms in cancer cells. Autophagy, 5, 432–433.

    Article  PubMed  Google Scholar 

  122. Bhutia, S. K., Mallick, S. K., & Maiti, T. K. (2009). In vitro immunostimulatory properties of Arbus lectins derived peptides in tumor bearing mice. Phytochemistry, 16, 776–782.

    CAS  Google Scholar 

  123. Ghosh, D., & Maiti, T. K. (2007). Effects of native and heat-denatured Abrus agglutinin on tumor-associated macrophages in Dalton’s lymphoma mice. Immunobiology, 212, 667–673.

    Article  CAS  PubMed  Google Scholar 

  124. Khil, L. Y., Kim, W., Lyu, S., Park, W. B., Yoon, J. W., & Jun, H. S. (2007). Mechanisms involved in Korean mistletoe lectin-induced apoptosis of cancer cells. World Journal of Gastroenterology, 13, 2811–2818.

    CAS  PubMed  Google Scholar 

  125. Ma, Y. H., Cheng, W. Z., Gong, F., Ma, A. L., Yu, Q. W., Zhang, J. Y., et al. (2008). Active Chinese mistletoe lectin-55 enhances colon cancer surveillance through regulating innate and adaptive immune responses. World Journal of Gastroenterology, 14, 5274–5281.

    Article  CAS  PubMed  Google Scholar 

  126. Monira, P., Koyoma, Y., Fukutomi, R., Yasui, K., Isemura, M., & Yokogoshi, H. (2009). Effects of Japanese mistletoe lectin on cytokine gene expression in human colonic carcinoma cells and in the mouse intestine. Biomedical Research, 30, 303–309.

    Article  CAS  PubMed  Google Scholar 

  127. Lyu, S. Y., & Park, W. B. (2009). Mistletoe lectin modulates intestinal epithelial cell-derived cytokines and B cell IgA secretion. Archives of Pharmacal Research, 32, 443–451.

    Article  CAS  PubMed  Google Scholar 

  128. Seifert, G., Jesse, P., Laengler, A., Reindl, T., Luth, M., Lobitz, S., et al. (2008). Molecular mechanisms of mistletoe plant extract-induced apoptosis in acute lymphoblastic leukemia in vivo and in vitro. Cancer Letters, 264, 218–228.

    Article  CAS  PubMed  Google Scholar 

  129. Lavaster, V., Chiasson, S., Cavalli, H., & Girard, D. (2005). Viscum album agglutinin-I (VAA-I) induces apoptosis and degradation of cytoskeletal protein in human leukemia PLB-985 and X-CGD cells via caspases: Lamin B1 is a novel target of VAA-I. Leukemia Research, 29, 1443–1453.

    Article  CAS  Google Scholar 

  130. Lavastre, V., Binet, F., Moisan, E., Chaisson, S., & Girard, D. (2007). Viscum album agglutinin-I induces degradation of cytoskeletal proteins in leukemia PLB-985 cells differentiated toward neutrophils: cleavage of non-muscle myosin heavy chain-IIA by caspases. British Journal Haematology, 138, 545–554.

    Article  CAS  Google Scholar 

  131. Kovacs, E., Link, S., & Toffol-Schmidt, U. (2008). Comparison of Viscum album QuFrF extract with vincristine in an in vitro model of human B cell lymphoma WSU-1. Arzneimittelforschung, 58, 592–597.

    CAS  PubMed  Google Scholar 

  132. Thies, A., Dautel, P., Meyer, A., Pfuller, U., & Schumacher, U. (2008). Low-dose mistletoe lectin-I reduces melanoma growth and spread in a scid mouse xenograft model. British Journal of Cancer, 98, 106–112.

    Article  CAS  PubMed  Google Scholar 

  133. Liu, B., Zhang, B., Min, M., Bian, H., Chen, L., Liu, Q., et al. (2009). Induction of apoptosis by Polygonatum odoratum lectin and its molecular mechanisms in murine fibrosarcoma L929 cells. Biochimica et Biophysica Acta, 1790, 840–844.

    CAS  PubMed  Google Scholar 

  134. Peng, H., Lv, H., Wang, Y., Liu, Y., Li, C., Meng, L., et al. (2009). Clematis Montana lectin, a novel mannose-binding lectin from traditional Chinese medicine with antiviral and apoptosis-inducing activities. Peptides, 30, 1805–1815.

    Article  CAS  PubMed  Google Scholar 

  135. Liu, Z., Liu, B., Zhang, Z. T., Zhou, T. T., Bian, H. J., Min, M. W., et al. (2008). A mannose-binding lectin from Sophora flavescens induces apoptosis in HeLa cells. Phytomedicine, 15, 867–875.

    Article  CAS  PubMed  Google Scholar 

  136. Freudlsperger, C., Thies, A., Pfuller, U., & Schumacher, U. (2007). The proteasome inhibitor bortezomib augments anti-proliferative effects of mistletoe lectin-I and the PPAR-γ agonist rosiglitazone in human melanoma cells. Anticancer Research, 27, 207–214.

    CAS  PubMed  Google Scholar 

  137. Sabova, L., Pilatova, M., Szilagyi, K., Sabo, R., & Mojzis, J. (2010). Cytotoxic effect of mistletoe (Viscum album L.) extract on Jurkat cells and its interaction with doxorubicin. Phytotherapy Research, 24, 365–368.

    Article  CAS  PubMed  Google Scholar 

  138. Hernandez-Ledesma, B., Hsieh, C. C., & de Lumen, B. O. (2009). Lunasin, a novel seed peptide for cancer prevention. Peptides, 30, 426–430.

    Article  CAS  PubMed  Google Scholar 

  139. Galvez, A. F., & de Lumen, B. O. (1999). A soybean cDNA encoding a chromatin-binding peptide inhibits mitosis of mammalian cells. Nature Biotechnology, 17, 495–500.

    Article  CAS  PubMed  Google Scholar 

  140. Galvez, A. F., Chen, N., Macasieb, J., & de Lumen, B. O. (2001). Chemopreventive property of a soybean peptide (lunasin) that binds to deacetylated histones and inhibits acetylation. Cancer Research, 61, 7473–7478.

    CAS  PubMed  Google Scholar 

  141. Hsieh, E. A., Chai, C. M., de Lumen, B. O., Neese, R. A., & Hellerstein, M. K. (2004). Dynamics of keratinocytes in vivo using (H2O)-H2 labeling: a sensitive marker of epidermal proliferation rate. The Journal of Investigative Dermatology, 123, 530–536.

    Article  CAS  PubMed  Google Scholar 

  142. Jeong, H. J., Park, J. H., Lam, Y., & de Lumen, B. O. (2003). Characterization of lunasin isolated from soybean. Journal of Agricultural and Food Chemistry, 51, 7901–7906.

    Article  CAS  PubMed  Google Scholar 

  143. Jeong, H. J., Lam, Y., & de Lumen, B. O. (2002). Barley lunasin suppresses ras-induced colony formation and inhibits core histone acetylation in mammalian cells. Journal of Agricultural and Food Chemistry, 50, 5903–5908.

    Article  CAS  PubMed  Google Scholar 

  144. Jeong, H. J., Jeong, J. B., Kim, D. S., Park, J. H., Lee, J. B., Kweon, D. H., et al. (2007). The cancer preventive peptide lunasin from wheat inhibits core histone acetylation. Cancer Letters, 255, 42–48.

    Article  CAS  PubMed  Google Scholar 

  145. Jeong, J. B., Jeong, H. J., Park, J. H., Lee, S. H., Lee, J. R., Lee, H. K., et al. (2007). Cancer-preventive peptide lunasin from Solanum nigrum L. inhibits acetylation of core histones H3 and H4 and phosphorylation of retinoblastoma protein (Rb). Journal of Agricultural and Food Chemistry, 55, 10707–10713.

    Article  CAS  PubMed  Google Scholar 

  146. Jeong, H. J., Lee, J. R., Joeng, J. B., Park, J. H., Cheong, Y. K., & de Lumen, B. O. (2009). The cancer preventive seed peptide lunasin from rye is bioavailable and bioactive. Nutrition and Cancer, 61, 680–686.

    Article  CAS  PubMed  Google Scholar 

  147. Silva-Sanchez, C., dela Rosa, A. P. B., Leon-Galvan, M. F., de Lumen, B. O., de Leon-Rodriguez, A., & de Mejia, E. G. (2008). Bioactive peptides from amaranth (Amaranthus hypochondriacus) seed. Journal of Agricultural and Food Chemistry, 56, 1233–1240.

    Article  CAS  PubMed  Google Scholar 

  148. Jeong, J. B., de Lumen, B. O., & Jeong, H. J. (2010). Lunasin peptide purified from Solanum nigrum L. protects DNA from oxidative damage by suppressing the generation of hydroxyl radical via blocking fenton reaction. Cancer Letters, 293, 58–64.

    Article  CAS  PubMed  Google Scholar 

  149. Lam, Y., Galvez, A., & de Lumen, B. O. (2003). Lunasin™ suppresses E1A-mediated transformation of mammalian cells but does not inhibit growth of immortalized and established cancer cell lines. Nutrition and Cancer, 47, 88–94.

    Article  CAS  PubMed  Google Scholar 

  150. Dia, V. P., Wang, W., Oh, V. L., de Lumen, B. O., & de Mejia, E. G. (2009). Isolation, purification and characterisation of lunasin from defatted soybean flour and in vitro evaluation of its anti-inflammatory activity. Food Chemistry, 114, 108–115.

    Article  CAS  Google Scholar 

  151. de Mejia, E. G., & Dia, V. P. (2009). Lunasin and lunasin-like peptides inhibit inflammation through suppression of NF-kappa B pathway in the macrophage. Peptides, 30, 2388–2398.

    Article  PubMed  CAS  Google Scholar 

  152. Hernandez-Ledesma, B., Hsieh, C. C., & de Lumen, B. O. (2009). Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasin in RAW 264.7 macrophages. Biochemical and Biophysical Research Communications, 390, 803–808.

    Article  CAS  PubMed  Google Scholar 

  153. de Mejia, E. G., Wang, W. Y., & Dia, V. P. (2010). Lunasin, with an arginine–glycine–aspartic acid motif, causes apoptosis to L1210 leukemia cells by activation of caspase-3. Molecular Nutrition & Food Research, 54, 406–414.

    Article  CAS  Google Scholar 

  154. Dia, V. P., & de Mejia, E. G. (2010). Lunasin promotes apoptosis in human colon cancer cells by mitochondrial pathway activation and induction of nuclear clusterin expression. Cancer Letters, 295, 44–53.

    Article  CAS  PubMed  Google Scholar 

  155. Hsieh, C. C., Hernandez-Ledesma, B., Jeong, H. J., Park, J. H., & de Lumen, B. O. (2010). Complementary roles in cancer prevention: protease inhibitor makes the cancer preventive peptide lunasin bioavailable. PLoS ONE, 5, e8890.

    Article  PubMed  CAS  Google Scholar 

  156. Dia, V. P., Torres, S., de Lumen, B. O., Erdman, J. W., & de Mejia, E. G. (2009). Presence of lunasin in plasma of men after soy protein consumption. Journal of Agricultural and Food Chemistry, 57, 1260–1266.

    Article  CAS  PubMed  Google Scholar 

  157. Yeh, C. L., Pai, M. H., Li, C. C., Tsai, Y. L., & Yeh, S. L. (2010). Effect of arginine on angiogenesis induced by human colon cancer: in vitro and in vivo studies. The Journal of Nutritional Biochemistry, 21, 539–543.

    Article  CAS  Google Scholar 

  158. Yeh, C. L., Hsu, C. S., Chen, S. C., Hou, Y. C., Chiu, W. C., & Yeh, S. L. (2007). Effect of arginine on cellular adhesion molecule expression and leukocyte transmigration in endothelial cells stimulated by biological fluid from surgical patients. Shock, 28, 39–44.

    Article  CAS  PubMed  Google Scholar 

  159. Chou, S. Y., Hsu, C. S., Hsu, M. Y., Liang, S. J., Yeh, C. L., & Yeh, S. L. (2009). Effects of different arginine concentrations on angiogenic protein production induced by HeLa cells. Nutrition, 26, 818–822.

    Article  CAS  Google Scholar 

  160. Rose, M. L., Madren, J., Bunzendahl, H., & Thruman, R. G. (1999). Dietary glycine inhibits the growth of B16 melanoma tumors in mice. Carcinogenesis, 20, 793–798.

    Article  CAS  PubMed  Google Scholar 

  161. Rose, M. L., Cattley, R. C., Dunn, C., Wong, V., Li, X., & Thurman, R. G. (1999). Dietary glycine prevents the development of liver tumors caused by the peroxisome proliferator WY-14, 643. Carcinogenesis, 20, 2075–2081.

    Article  CAS  PubMed  Google Scholar 

  162. Yoshiji, J., Noguchi, R., Kaji, K., Ikenaka, Y., Shirai, Y., Namisaki, T., et al. (2010). Attenuation of insulin-resistance-based hepatocarcinogenesis and angiogenesis by combined treatment with branched-chain amino acids and angiotensin-converting enzyme inhibitor in obese diabetic rats. Journal of Gastroenterology, 45, 443–450.

    Article  CAS  PubMed  Google Scholar 

  163. Kobayashi, H., Yoshida, R., Kanada, Y., Fukuda, Y., Yagyu, T., Inagaki, K., et al. (2005). Suppression of lipopolysaccharide-induced cytokine production of gingival fibroblasts by a soybean, Kunitz trypsin inhibitor. Journal of Periodontal Research, 40, 461–468.

    Article  CAS  PubMed  Google Scholar 

  164. Kobayashi, H., Yoshida, R., Kanada, Y., Fukuda, Y., Yagyu, T., Inagaki, K., et al. (2005). A soybean Kunitz trypsin inhibitor reduces tumor necrosis factor-α production in ultraviolet-exposed primary human keratinocytes. Experimental Dermatology, 14, 765–774.

    Article  CAS  PubMed  Google Scholar 

  165. Lei, H. Y., & Chang, C. P. (2007). Induction of autophagy by concanavalin A and its application in anti-tumor therapy. Autophagy, 3, 402–404.

    CAS  PubMed  Google Scholar 

  166. Liu, B., Cheng, Y., Bian, H. J., & Bao, J. K. (2009). Molecular mechanisms of Polygonatum cyrtonema lectin-induced apoptosis and autophagy in cancer cells. Autophagy, 5, 253–255.

    Article  CAS  PubMed  Google Scholar 

  167. Liu, B., Cheng, Y., Zhang, B., Bian, H. J., & Bao, J. K. (2009). Polygonatum cyrtonema lectin induces apoptosis and autophagy in human melanoma A375 cells through a mitochondria-mediated ROS-p38–p53 pathway. Cancer Letters, 275, 54–60.

    Article  CAS  PubMed  Google Scholar 

  168. Chang, C. P., & Lei, H. Y. (2008). Autophagy induction in T cell-independent acute hepatitis induced by concanavalin A in scid/nod mice. International Journal of Immunopathology and Pharmacology, 21, 817–826.

    CAS  PubMed  Google Scholar 

  169. Augustin, M., Bock, P. R., Hanisch, J., Karasmann, M., & Schneider, B. (2005). Safety and efficacy of the long term adjuvant treatment of primary intermediate- to high-risk malignant melanoma (UICC/AJCC stage II and III) with a standardized fermented European mistletoe (Viscum album L.) extract—results from a multicenter, comparative, epidemiological cohort study in Germany and Switzerland. Arzneimittelforschung, 55, 38–49.

    CAS  PubMed  Google Scholar 

  170. Mabed, M., El-Helw, L., & Shamaa, S. (2004). Phase II study of viscum fraxini-2 in patients with advanced hepatocellular carcinoma. British Journal of Cancer, 90, 65–69.

    Article  CAS  PubMed  Google Scholar 

  171. Schoffski, P., Riggert, S., Fumoleau, P., Campone, M., Bolte, O., Marreaud, S., et al. (2004). Phase I trial of intravenous aviscumine (rViscumin) in patients with solid tumors: a study of the European Organization for Research and Treatment of Cancer New Drug Development Group. Annals of Oncology, 15, 1816–1824.

    Article  CAS  PubMed  Google Scholar 

  172. Malkowicz, S. B., McKenna, W. G., Vaughn, D. J., Wan, X. S., Propert, K. J., Rockwell, K., et al. (2001). Effects of Bowman–Birk inhibitor concentrate (BBIC) in patients with benign prostatic hyperplasia. The Prostate, 48, 16–28.

    Article  CAS  PubMed  Google Scholar 

  173. Armstrong, W. B., Kennedy, A. R., Wan, X. S., Atiba, J., McLaren, E., & Meyskens, F. L. (2000). Single-dose administration of Bowman–Birk inhibitor concentrate in patients with oral leukoplakia. Cancer Epidemiology, Biomarkers & Prevention, 9, 43–47.

    CAS  Google Scholar 

  174. Armstrong, W. B., Kennedy, A. R., Wan, X. S., Taylor, T. H., Nguyen, Q. A., Jensen, J., et al. (2000). Clinical modulation of oral leukoplakia and protease activity by Bowman–Birk inhibitor concentrate in a phase IIa chemoprevention trial. Clinical Cancer Research, 6, 4684–4691.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the funding from the Illinois Soybean Association and the US Department of Agriculture World Food Initiative.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elvira Gonzalez de Mejia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Mejia, E.G., Dia, V.P. The role of nutraceutical proteins and peptides in apoptosis, angiogenesis, and metastasis of cancer cells. Cancer Metastasis Rev 29, 511–528 (2010). https://doi.org/10.1007/s10555-010-9241-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-010-9241-4

Keywords

Navigation