An Alpha-fetoprotein derived Peptide Suppresses Growth in Breast Cancer and Other Malignancies: A Review and Prospectus
Main Article Content
Abstract
Growth Inhibitory Peptide (GIP) is an alpha-fetoprotein (AFP) derived peptide found during human pregnancy, which gradually disappears following childbirth in both the woman and the newborn. Following a stress-induced conformational change in the AFP molecule, GIP is exposed on the protein surface from a concealed occult site on the unfolded full-length AFP. The exposed 34-amino acid GIP peptide then targets, blocks, and suppresses malignant growth in the mammalian body. In the present report, GIP has been demonstrated to inhibit cell growth in vitro in nine different types of cancers including breast, prostate, and ovarian among others. GIP can further assist in preventing blood clotting, arresting growth via the cytoplasmic growth cycle, suppressing tumor blood vessel angiogenesis, and inhibiting circulating cancer cell metastasis. In further studies, GIP has been reported to suppress cancer growth in 38 of 60 different cancer cell culture lines. The growth suppressed human breast cancer cell lines included MCF-7, T-47D, Bt-547, MDA-MB-231, MDA-MB-435, in addition to mouse mammary tumor implants and xenografts. Thus, GIP was found to suppress and inhibit cancer growth in both in vitro and in vivo preclinical studies.
Keywords:
Alpha-fetoprotein, oncofetal protein, growth regulation, cell cycle, breast cancer, prostate cancer, malignancy, metastasis
Article Details
How to Cite
MIZEJEWSKI, Dr. Gerald J..
An Alpha-fetoprotein derived Peptide Suppresses Growth in Breast Cancer and Other Malignancies: A Review and Prospectus.
Medical Research Archives, [S.l.], v. 11, n. 7.2, july 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4147>. Date accessed: 15 may 2024.
doi: https://doi.org/10.18103/mra.v11i7.2.4147.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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26. Mizejewski GJ. Breast cancer and transient receptor potential (TRCP) cation channels: Is there a role for non-selective TRP channels as therapeutic cancer targets: a commentary. Intl. Journal of Cancer Res. And Development. 2017. 2:4-6.
27. Mizejewski GJ. The third domain fragments of alpha-fetoprotein (AFP): mapping AFP interactions with selective and non-selective cation channels. Curr. Topics Peptide Protein Res. (in press) 2016.
28. Mizejewski GJ. Cancer, circulating tumor cells, and metastasis: could protein-derived peptide fragments impede brain metastasis? Journal of Cancer Metastasis and Treatment, 2018. 10:205-225.
29. Mizejewski GJ. Disintergrin-like peptides derived from naturally occurring proteins: a proposed adjunct treatment for cancer therapy. Intl J Res Mol. Mech. 2020. 5(2): 2381-3318.
30. Mizejewski GJ. Antimicrobial peptides and cancer: potential use of antimicrobial-like peptides in chemotherapy. J. Cancer Biol. Therap. 2019. 5:233-242.
31. Mizejewski GJ. Cell-penetrating versus antimicrobial peptides: comparison of potential use as cancer therapeutics Journal of Oncology Research Forecast. 2019 2:1013-1015.
32. Mizejewski GJ, Muehlemann M, Dauphiee M. Update of alpha fetoprotein growth inhibitory peptides as biotherapeutic agents for tumor growth and metstasis. Chemotherapy 2006. 52(2): 83-90.
33. Vakharia D. Mizejewski GJ. Human alpha-fetoprotein peptides bind estrogen receptor and estradiol and suppress breast cancer. Breast Cancer Res. Treat. 2000. 63(1):41-52.
34. Mikhail Bogdanov, Jun Xie, Phil Heacock, William Dowham. To flip or not to flip: lipid-protein charge interactions are a determinant of final membrane protein topology. J Cell Biol. 2008 Sep 8; 182(5):925-35.
35. Mizejewski GJ. Review of the adenocarcinoma cell surface receptor for human alpha-fetoprotein; propsea identification of a widespread mucin as a the tumor cell receptor. Tumour Viol. 2013. 34(3):1317-1336.
36. Mizejewski GJ. The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets. J. Drug Target. 2015. 23(6):538-551.
37. Mizejewski GJ. Alpha-fetoprotein (AFP)-derived peptides as epitopes for hepatoma immunotherapy: a commentary. Cancer Immunol. Immunother. 2019. 58(2):159-170.
38. Butterfield LH, Ribas A, Dissette VB, Lee Y, Yang JQ, et al. A phase I/II trial testing immunization of hepatocellular carcinoma patients with dendritic cells pulsed with four alpha-fetoprotein peptides. Clin. Cancer Res. 2006. 1: 2817-2825
39. Butterfield LH, Koh A, Meng W, Vollmer CM, Ribas A, et l. (1999) Generation of human T-cell responses to an HLA-A2. 1-restricted peptide epitope derived from alpha-fetoprotein. Cancer Res 1999. 59: 3134-3142.
40. Zhang C, Jiang W, Li H, Hou W, Li G: “Enhanced Hepatoma-cell GIP-36, Peking University Chinese Patent filing, number CN201410166756.3A/B, 2014, patent pending.
41. Richardson BE, Hulka BS, David Peck JL, Huges CL, van den Berg BJ, Christianson RE, Calvin JA. Levels of maternal serum alpha-fetoprotein (AFP) in pregnant women and subsequent breast cancer risk. Am L Epidemiol 148:719-727.1998
42. Gasic GJ, Gasic TB, Galanti N, Johnson N, Murphy S. Platelet-tumor-cell interactions in mice. The role of platelets in the spread of malignant disease. Int J Cancer. 1993. 11:704-718.
2. Mizejewski, G.J. Alpha-fetoprotein as a biologic response modifier: relevance to domain and subdomain structure. Proc. Soc. Exp. Biol. Med. 1997. 215(4):333-362.
3. Luft, A.J., Lorscheider, F.L., Structural analysis of human and bovine AFP by election microscopy, image processing, and circular dichoism. Biochem. 1983 22:5978-5981.
4. Mizejewski, G.J. Biological roles of aloha-fetoprotein during pregnancy and perinatal development. Exp. Biol. Med. 2004. 229(6): 439-463.
5. Mizejewski, G.J. Physiology of alpha-fetoprotein as a biomarker for perinatal distress: relevance to adverse pregnancy outcome. Exp. Biol. Med. 2007. 232(8):993-1004.
6. Mizejewski, G.J, Head and neck germ cell tumors: effectiveness of alpha-fetoprotein as a diagnostic biomarker, BAOJ Cancer Research & Therapy. 2017. 4:52-58
7. Mizejewski, G.J, Breast Cancer, metastasis, and the microenvironment: disabling the tumor cell-to-stroma communication network, Journal of Cancer Metastasis and Treatment, 2019 Doi: 10.20517/2394-4722.2018.70.
8. Mizejewski, G.J. Breast Cancer, chemokines, and metastasis: a search for decoy ligands of the CXCR4 receptor. Journal Neoplasms. 2018 1:1-5.
9. Mizejewski, G.J. Should “transformed alpha-fetoprotein” be considered a potential biomarker for adverse term pregnancy risk: an opinion letter. Gynecology and Women’s Health Care. 2020 2:1-6.
10. Ingham KC, Brew SA, Erickson HP: Localization of a cryptic binding site for tenascin of fibronectin. J Biol Chem 2004. 279: 28132-28135
11. Podolnikova NP, Yakubenko VP, Volkov GL, Plow EF, Ugarova TP: Identification of a novel binding site for platelet integrins alpha IIb beta 3 (GPIIbIIIa) and alpha 5 beta 1 in the gamma C-domain of fibrinogen. J Biol chem. 2003. 278: 32251-32258
12. Uversky NV, Kirkitadze MD, Narizhneva NV, Potekhin SA, Tomashevski AY. Structural properties of AFP from human cord serum: The protein molecule at low pH possess all the properties of the molten globule FEBS Lett. 1995. 364: 165-176.
13. Uversky NV. Narizhneva NV, Ivanova TV, Tomashevski AY. Rigidity og human AFP tertiary, structure is under ligand control. Biochemistry. 1997. 36:13638-13645
14. Dudich IV, Semenkova LN, Dudich EI. Reversible conformational changes in the teritary structure of the human AFP molecule induced by ligand-protein and protein-protein interactions. Tumor Biol 1990. 19:34
15. Muehlemann M, Miller KD, Dauphinee M, Mizejewski GJ. Review of Growth Inhibitory Peptide as a biotherapeutic agent for tumore growth, adhesion, and metastasis. Cancer Metastasis rev. 2005. 24:441-467
16. Mizejewski GJ, Butterstein G. Survey of functional activities of alpha-fetoprotein derived growth inhibitory peptides: Review and Prospects. Curr Protein Pept Sci. 2006. 7:73-100.
17. Bennassayag C, Rigoud V, Hassid J, Nunez EA. Does high polyunsaturated free fatty acid level at the feta-maternal interface alter steroid hormone message during pregnancy? Prostaglandins, Luekoirienes and Essential Fatty Acids. 1999. 60(5-6).393-399.
18. Vallete G, Martin ME, Benassayog C, Nunez EA (1989). Conformational changes in rodent and human alpha-fetoprotein: Influnece of fatty acids at biophysics Acto (BBA)- Protein structure and molecule EnzymoLogy. 1997(3): 302-312.
19. Mizejewski GJ, MacColl R. Alpha-fetoprotein growth inhibitory peptides: Potential leads for cancer therapeutics. Mol Cancer Ther. 2003. 2: 1243-1255.
20. Mizejewski GJ, Mirowski M, Garnuszek P, Maurin M, Cohen B.D, Poiesz BJ, Posypanova, GA, Makarov, VA, Severin ES, Severin SE. Targeted delivery of anti-cancer growth inhibitory peptides derived from human alpha-fetoprotein: review of an International Muilt-Center Collaborative Study. J. Drug Target. 2010. 18(8):575-588.
21. Mizejewski GJ, (2011) Mechanism of cancer growth suppression of alpha-fetoprotein derived growth inhibitory peptides (GIP): Comparison of GIP-34 versus GIP-8 (AFPPep). Updates and Prospects. Cancers. 2011. 3(2):2709-2733.
22. Mizejewski GJ, Smith G, Butterstein G. Review and proposed action of alpha-fetoprotein growth inhibitory peptides as estrogen and cytoskeleton-associated factors. Cel Biol. Int. 2004. 28(12):913-933.
23. Mizejewski GJ. The alpha-fetoprotein (AFP) third domain: a search of AFP interaction sites of cell cycle proteins. Tumor Biol. 2016 37(9):12697-711. Epub 2016/10/27.
24. Mizejewski GJ. Breast Cancer and cell cycle inhibitors (CCIs): potential therapeutic strategies for CCI cell targeting and drug delivery. Current Advances in Oncology Res. & Therapy (Issue-1) 2019: 1-8.
25. Mizejewski GJ. The third domain ligand binding fragment of alpha-fetoprotein: detection of Metastasis-associated molecular targets. Cancer Therapy & Oncology. 2017 6:1-8.
26. Mizejewski GJ. Breast cancer and transient receptor potential (TRCP) cation channels: Is there a role for non-selective TRP channels as therapeutic cancer targets: a commentary. Intl. Journal of Cancer Res. And Development. 2017. 2:4-6.
27. Mizejewski GJ. The third domain fragments of alpha-fetoprotein (AFP): mapping AFP interactions with selective and non-selective cation channels. Curr. Topics Peptide Protein Res. (in press) 2016.
28. Mizejewski GJ. Cancer, circulating tumor cells, and metastasis: could protein-derived peptide fragments impede brain metastasis? Journal of Cancer Metastasis and Treatment, 2018. 10:205-225.
29. Mizejewski GJ. Disintergrin-like peptides derived from naturally occurring proteins: a proposed adjunct treatment for cancer therapy. Intl J Res Mol. Mech. 2020. 5(2): 2381-3318.
30. Mizejewski GJ. Antimicrobial peptides and cancer: potential use of antimicrobial-like peptides in chemotherapy. J. Cancer Biol. Therap. 2019. 5:233-242.
31. Mizejewski GJ. Cell-penetrating versus antimicrobial peptides: comparison of potential use as cancer therapeutics Journal of Oncology Research Forecast. 2019 2:1013-1015.
32. Mizejewski GJ, Muehlemann M, Dauphiee M. Update of alpha fetoprotein growth inhibitory peptides as biotherapeutic agents for tumor growth and metstasis. Chemotherapy 2006. 52(2): 83-90.
33. Vakharia D. Mizejewski GJ. Human alpha-fetoprotein peptides bind estrogen receptor and estradiol and suppress breast cancer. Breast Cancer Res. Treat. 2000. 63(1):41-52.
34. Mikhail Bogdanov, Jun Xie, Phil Heacock, William Dowham. To flip or not to flip: lipid-protein charge interactions are a determinant of final membrane protein topology. J Cell Biol. 2008 Sep 8; 182(5):925-35.
35. Mizejewski GJ. Review of the adenocarcinoma cell surface receptor for human alpha-fetoprotein; propsea identification of a widespread mucin as a the tumor cell receptor. Tumour Viol. 2013. 34(3):1317-1336.
36. Mizejewski GJ. The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets. J. Drug Target. 2015. 23(6):538-551.
37. Mizejewski GJ. Alpha-fetoprotein (AFP)-derived peptides as epitopes for hepatoma immunotherapy: a commentary. Cancer Immunol. Immunother. 2019. 58(2):159-170.
38. Butterfield LH, Ribas A, Dissette VB, Lee Y, Yang JQ, et al. A phase I/II trial testing immunization of hepatocellular carcinoma patients with dendritic cells pulsed with four alpha-fetoprotein peptides. Clin. Cancer Res. 2006. 1: 2817-2825
39. Butterfield LH, Koh A, Meng W, Vollmer CM, Ribas A, et l. (1999) Generation of human T-cell responses to an HLA-A2. 1-restricted peptide epitope derived from alpha-fetoprotein. Cancer Res 1999. 59: 3134-3142.
40. Zhang C, Jiang W, Li H, Hou W, Li G: “Enhanced Hepatoma-cell GIP-36, Peking University Chinese Patent filing, number CN201410166756.3A/B, 2014, patent pending.
41. Richardson BE, Hulka BS, David Peck JL, Huges CL, van den Berg BJ, Christianson RE, Calvin JA. Levels of maternal serum alpha-fetoprotein (AFP) in pregnant women and subsequent breast cancer risk. Am L Epidemiol 148:719-727.1998
42. Gasic GJ, Gasic TB, Galanti N, Johnson N, Murphy S. Platelet-tumor-cell interactions in mice. The role of platelets in the spread of malignant disease. Int J Cancer. 1993. 11:704-718.