The DOI matches its Crossref record.
Novel Anticancer Activity of the Autocleaved Ovotransferrin against Human Colon and Breast Cancer Cells
Abstract
Proteins of avian egg albumin have been suggested to play various biological roles during the development of chick embryo to confer protection. Recently, we have shown that ovotransferrin (OTf), the second major protein in egg albumin, undergoes thiol-linked autocleavage at distinct sites upon reduction. This study explores the physiological significance of OTf autocleavage by examining the effect of the reduced autocleaved OTf (termed rac-OTf) on modulation of cell proliferation, lethality, and apoptosis in two human cancer cell lines, colon cancer (HCT-116) and breast cancer (MCF-7). The rac-OTf was prepared by reduction of OTf with a non-thiol reductant (TCEP), to avoid reductive alkylation and produce highly soluble fragments. Unlike OTf, rac-OTf remarkably inhibited the proliferation of cancerous MCF-7 and HCT-116 cells in a dose-dependent manner, with the greatest effect on HCT-116, but had no effect on normal human mammary epithelial cells (HMEC). Cytofluorometric and trypan blue exclusion analyses indicated that rac-OTf exhibits cytotoxicity to HCT-116 in a dose-dependent fashion. The cytotoxic mechanism of rac-OTf against cancer cells was found to be induction of apoptosis as judged by changes in cell morphology, annexin-V binding, collapse of mitochondrial membrane potential, and caspase-9 and -6 activation, indicating the involvement of the mitochondrial pathway. This finding is the first to describe the reduction-dependent autocleaved OTf as an anticancer molecule…
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Partially hydrolyzed products of ovotransferrin have very strong anticancer effects against colon and breast cancer cells.
“Ibrahim and Kiyono (2009) reported that ovotransferrin underwent thiol-linked auto-cleavage after reduction, and produced partially hydrolyzed products with very strong anticancer effects against colon and breast cancer cells.”
From Egg white proteins and their potential use in food processing or as nutraceutical and pharmaceutical agents—A review (2013) · cites this paper as Ibrahim and Kiyono, 2009
Ovotransferrin undergoes thiol-linked auto-cleavage after reduction.
“Ibrahim and Kiyono (2009) reported that ovotransferrin underwent thiol-linked auto-cleavage after reduction, and produced partially hydrolyzed products with very strong anticancer effects against colon and breast cancer cells.”
From Egg white proteins and their potential use in food processing or as nutraceutical and pharmaceutical agents—A review (2013) · cites this paper as Ibrahim and Kiyono, 2009
Citations
Cites
Still being checked.
Cited by
Sorted by citations
The Golden Egg: Nutritional Value, Bioactivities, and Emerging Benefits for Human Health
Réhault‐Godbert, S., Guyot, N., & Nys, Y. Y. (2019) · Nutrients · doi:10.3390/nu11030684 · Cited by 703
Abeyrathne, E. D. N. S., Lee, H. Y., & Ahn, D. U. (2013) · Poultry Science · doi:10.3382/ps.2013-03391 · Cited by 532
Ovotransferrin: Structure, bioactivities, and preparation
Wu, J., & Acero-Lopez, A. (2012) · Food Research International · doi:10.1016/j.foodres.2011.07.012 · Cited by 188
Physiological roles of ovotransferrin
Giansanti, F., Leboffe, L., Pitari, G., Ippoliti, R., & Antonini, G. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.08.004 · Cited by 145
Assembly of iron-bound ovotransferrin amyloid fibrils
Wei, Z., & Huang, Q. (2018) · Food Hydrocolloids · doi:10.1016/j.foodhyd.2018.11.028 · Cited by 129
Abeyrathne, E. D. N. S., Huang, X., & Ahn, D. U. (2018) · Poultry Science · doi:10.3382/ps/pex399 · Cited by 107
An insight on egg white: From most common functional food to biomaterial application
Dong, X., & Zhang, Y. (2020) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.34768 · Cited by 107
Anticancer and immunomodulatory activity of egg proteins and peptides: a review
Lee, J. H., & Paik, H. (2019) · Poultry Science · doi:10.3382/ps/pez381 · Cited by 82
Functional properties of ovotransferrin from chicken egg white and its derived peptides: a review
Rathnapala, E. C. N., Ahn, D. U., & Abeyrathne, E. D. N. S. (2021) · Food Science and Biotechnology · doi:10.1007/s10068-021-00901-3 · Cited by 67
Natural Products of Plants and Animal Origin Improve Albumen Quality of Chicken Eggs
Obianwuna, U. E., Oleforuh-Okoleh, V. U., Wang, J., Zhang, H., Qi, G., Qiu, K., & Wu, S. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.875270 · Cited by 67
Ovotransferrin enhances intestinal immune response in cyclophosphamide-induced immunosuppressed mice
Zhu, G., Luo, J., Du, H., Jiang, Y., Tu, Y., Yao, Y., & Xu, M. (2018) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2018.08.058 · Cited by 66
The Nutraceutical Properties of Ovotransferrin and Its Potential Utilization as a Functional Food
Giansanti, F., Leboffe, L., Angelucci, F., & Antonini, G. (2015) · Nutrients · doi:10.3390/nu7115453 · Cited by 61
Antioxidant and anticancer effects of functional peptides from ovotransferrin hydrolysates
Lee, J. H., Moon, S. H., Kim, H. S., Park, E., Ahn, D. U., & Paik, H. (2017) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.8356 · Cited by 58
Effect of high pressure treatment on ovotransferrin
Acero‐Lopez, A., Ullah, A., Offengenden, M., Jung, S., & Wu, J. (2012) · Food Chemistry · doi:10.1016/j.foodchem.2012.07.071 · Cited by 57
Antioxidant effects of ovotransferrin and its hydrolysates
Kim, J., Moon, S.-H., Ahn, D. U., Paik, H., & Park, E. (2012) · Poultry Science · doi:10.3382/ps.2012-02150 · Cited by 48
The past and future of ovotransferrin: Physicochemical properties, assembly and applications
Wang, X., Wei, Z., & Xue, C. (2021) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2021.07.003 · Cited by 48
Separation of ovotransferrin and ovomucoid from chicken egg white
Abeyrathne, E. D. N. S., Lee, H. Y., & Ahn, D. U. (2014) · Poultry Science · doi:10.3382/ps.2013-03649 · Cited by 47
Khan, M. V., Ishtikhar, M., Rabbani, G., Zaman, M., Abdelhameed, A. S., & Khan, R. H. (2016) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2016.10.023 · Cited by 46
Fluoroalcohols-induced modulation and amyloid formation in conalbumin
Khan, M. V., Rabbani, G., Ahmad, E., & Khan, R. H. (2014) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2014.07.027 · Cited by 39
Screening for cytotoxic activity of ovotransferrin and its enzyme hydrolysates
Moon, S. H., Lee, J. H., Lee, Y. J., Chang, K. H., Paik, J. Y., Ahn, D. U., & Paik, H. D. (2013) · Poultry Science · doi:10.3382/ps.2012-02680 · Cited by 36
Khan, M. V., Rabbani, G., Ishtikhar, M., Khan, S., Saini, G., & Khan, R. H. (2015) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2015.04.021 · Cited by 34
Moon, S. H., Lee, J. H., Kim, J. H., Paik, H., & Ahn, D. U. (2017) · Poultry Science · doi:10.3382/ps/pew459 · Cited by 29
Jiang, K., Wang, C., Sun, Y., Liu, Y., Zhang, Y., Huang, L., & Wang, Z. (2014) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf501352j · Cited by 29
An Extensive Description of the Peptidomic Repertoire of the Hen Egg Yolk Plasma
Arena, S., & Scaloni, A. (2018) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.8b01183 · Cited by 27
Obianwuna, U. E., Chang, X., Wang, J., Zhang, H., Qi, G., Qiu, K., & Wu, S. (2022) · Foods · doi:10.3390/foods11131828 · Cited by 24
A novel antibiotic-delivery system by using ovotransferrin as targeting molecule
Ibrahim, H. R., Tatsumoto, S., Ono, H., Immerseel, F. V., Raspoet, R., & Miyata, T. (2014) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2014.10.005 · Cited by 23
Self-citationIn vitro antioxidant and mineral‐chelating properties of natural and autocleaved ovotransferrin
Moon, S. H., Lee, J. H., Ahn, D. U., & Paik, H. (2014) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.6921 · Cited by 23
Recent Advances in Applications of Bioactive Egg Compounds in Nonfood Sectors
Zhang, X., Chelliappan, B., Rajeswari, S., & Antonysamy, M. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.738993 · Cited by 22
Enzymatic Hydrolysis of Ovotransferrin and the Functional Properties of Its Hydrolysates
Rathnapala, E. C. N., Ahn, D. U., & Abeyrathne, E. D. N. S. (2021) · Food Science of Animal Resources · doi:10.5851/kosfa.2021.e19 · Cited by 18
Shang, N., Bhullar, K. S., & Wu, J. (2020) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.0c04064 · Cited by 17
Antioxidant, Antimicrobial, and Cytotoxic Activities of Ovotransferrin from Egg White
Moon, S.-H., Lee, J. H., Lee, Y.-J., Paik, J.-Y., Ahn, D.-U., & Paik, H. (2012) · Korean Journal for Food Science of Animal Resources · doi:10.5851/kosfa.2012.32.5.612 · Cited by 17
The Iron Binding Ability Maps the Fate of Food-Derived Transferrins: A Review
Chen, X., Zhang, X., Wu, Y., Wang, Z., Tian, Y., Chen, P., Tong, P., Gao, J., & Chen, H. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c04827 · Cited by 14
Ovotransferrin—Multifunctional protein: Structure, bioactivity, and industrial potential
Fijałkowski, P., Pryshchepa, O., van Eldik, R., & Pomastowski, P. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.144810 · Cited by 10
Nutraceuticals and cosmeceuticals: An overview
Rangaraj, S., Sasikanth, V., Ammashi, S., & Rathinavel, T. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-19193-0.00004-6 · Cited by 10
Zhou, Y., Tang, Q., Du, H., Tu, Y., Shao-fu, W., Wang, W., & Xu, M. (2018) · Food and Agricultural Immunology · doi:10.1080/09540105.2018.1424120 · Cited by 10
Mohanty, S., Panda, S., Devadharshini, U., & Paul, S. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188862 · Cited by 10
Iron Transport Tocopheryl Polyethylene Glycol Succinate in Animal Health and Diseases
Srivastava, A., Lall, R., Talukder, J., DuBourdieu, D., & Gupta, R. C. (2019) · Molecules · doi:10.3390/molecules24234289 · Cited by 9
Expression of Ovotransferrin Enhances Tolerance of Yeast Cells toward Oxidative Stress
Ibrahim, H. R., Hozono, A., Fukami, M., Shaban, M. A., & Miyata, T. (2013) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf401152e · Cited by 8
Self-citationKinoshita, K., Myint, S. L., Shimogiri, T., Ibrahim, H. R., Kawabe, K., Okamoto, S., Lee, Y.-P., Matsuda, Y., & MAEDA, Y. (2016) · The Journal of Poultry Science · doi:10.2141/jpsa.0160055 · Cited by 8
Self-citationAbeyrathne, E. D. N. S., & Ahn, D. U. (2015) · Wageningen Academic Publishers eBooks · doi:10.3920/978-90-8686-804-9_2 · Cited by 8
Double-Edged Sword Effect of Diet and Nutrition on Carcinogenic Molecular Pathways in Breast Cancer
Neagu, A.-N., Josan, C.-L., Jayaweera, T. M., Weraduwage, K., Nuru, N., & Darie, C. C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252011078 · Cited by 7
Preparation and Immunological Reactions of a Purified Egg Allergen Ovotransferrin
Tong, P., Gao, J., Chen, H., Li, X., Zhang, Y., & Jian, S. (2013) · International Journal of Food Properties · doi:10.1080/10942912.2011.631249 · Cited by 7
Prasad, S., Patel, B. B., Kumar, P., Kaufman, J., & Lall, R. (2025) · Veterinary Sciences · doi:10.3390/vetsci12060514 · Cited by 6
Wang, H., Zhao, S.-X., Li, J., & Zhang, Y. (2023) · ACS Omega · doi:10.1021/acsomega.3c05810 · Cited by 6
Nolasco, E., Guha, S., & Majumder, K. (2019) · Royal Society of Chemistry eBooks · doi:10.1039/9781788013833-00223 · Cited by 6
Monji, H., Zand, H., Ghorbani, A., & Pourvali, K. (2022) · Nutrition and Cancer · doi:10.1080/01635581.2022.2085754 · Cited by 5
Piagette, J. T., Júnior, J. E. G. P., Kanaan, S. H. H., Herrera, C. T., Bastilhos, L. O., Peçanha, F. M., Vassallo, D. V., Miguel, M., & Wiggers, G. A. (2023) · Journal of Functional Foods · doi:10.1016/j.jff.2023.105529 · Cited by 4
Ovotransferrin as a novel drug-targeting molecule for cancer chemotherapy
Ibrahim, H. R., Miyawaki, D., & Miyata, T. (2020) · Journal of Stem Cell Research and Medicine · doi:10.15761/jscrm.1000141 · Cited by 3
Self-citationLeke, J. R., Wantasen, E., Siahaan, R., & Sompie, F. N. (2022) · ANIMAL PRODUCTION · doi:10.20884/1.jap.2022.24.2.115 · Cited by 3
Lisozima: Actividad antibacteriana y alergenicidad
Carrillo, W. (2013) · Cited by 2
Innate Antimicrobial Proteins and Peptides of Avian Egg
Ibrahim, H. R. (2019) · Royal Society of Chemistry eBooks · doi:10.1039/9781788013833-00211 · Cited by 2
Self-citationAdvances in the Separation of Functional Egg Proteins – Egg White Proteins
Abeyrathne, E. D. N. S., Huang, X., & Ahn, D. U. (2019) · Royal Society of Chemistry eBooks · doi:10.1039/9781788013833-00329 · Cited by 2
The Potential of Egg White Ovotransferrin as a Functional Food Ingredient against Osteoporosis
Shang, N. (2019) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3-5njv-av60 · Cited by 2
Sujiwo, J., Choo, H.-J., Kim, H.-J., Lee, J.-H., Lee, O., Kim, C. H., & Jang, A. (2026) · Poultry Science · doi:10.1016/j.psj.2026.107038 · Cited by 1
Function and Separation of Ovotransferrin from Chicken Egg
Abeyrathne, E. D. N. S., & Ahn, D. U. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-800879-9.00023-8 · Cited by 1
Hatta, H., Wang, Y., & Shen, J. (2018) · Advance Journal of Food Science and Technology · doi:10.19026/ajfst.14.5912 · Cited by 1
Carbohydrates, Proteins, and Amino Acids
Sudha, S., Inbathamizh, L., & Prabavathy, D. (2022) · Wiley eBooks · doi:10.1002/9781119746843.ch25 · Cited by 1
Monji, H., Zand, H., Ghorbani, A., & Pourvali, K. (2021) · Research Square · doi:10.21203/rs.3.rs-953583/v1
Proteínas de origem animal: propriedades fisiológico-funcionais
Sgarbieri, V. C. (2020) · Editora da Unicamp eBooks · doi:10.7476/9788526815933.0007
Development of high protein beverage from hydrolyzed egg white
Charoensak, N. (2022) · Chula Digiverse · doi:10.58837/chula.the.2022.161
Metadata
- Authors
- Ibrahim, H. R., & Kiyono, T.
- Affiliations
- Kagoshima University (JP)
- National Cancer Center Research Institute (JP)
- Corresponding author
- Ibrahim, Hisham R.
- Venue
- Journal of Agricultural and Food Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2009-12-09
- Volume
- 57
- Issue
- 23
- Pages
- 11383-11390
- ISSN
- 0021-8561 (ISSN-L)
- 1520-5118
- OpenAlex
- W2043270798
- Cited by
- 61
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 5 · 2012: 3
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Agricultural and Food Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Research Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Keywords
- ovotransferrin, autocleavage, ovalbumin, anticancer activity, colon cancer, breast cancer, apoptosis, mitochondrial apoptosis, caspase activation, cytotoxicity, cell proliferation inhibition, nutraceuticals, TCEP reduction
- MeSH terms
- Animals, Antineoplastic Agents, Breast Neoplasms, Chickens, Colonic Neoplasms, Conalbumin, Humans, Apoptosis, HCT116 Cells, Cell Line, Tumor, Cell Proliferation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review