Progress 10/01/05 to 09/30/10
Outputs
OUTPUTS: We continue to define the molecular mechanisms of lunasin as a cancer preventative. Lunasin is bioavailable in men when administered orally with soymilk. To explain its bioavalability, we showed in a mouse and an in vitro model, that lunasin is protected from digestion by naturally occurring protease inhibitors in soy protein. In a mouse xenograft model, lunasin is preventive against breast cancer. Lunasin has also anti-inflammatory and anti-oxidant properties. In addition to its presence in soybean, we report that lunasin is present in rye, Solanum nigrum family, amaranth and barley. PARTICIPANTS: C. Silva-Sanchez, Scientist, Molecular Biology Division, Instituto Potosino de Investigacion Cientifica y Tecnologica, San Luis Potosi, S.L.P., Mexico, Research interest: bioactive components in native Mexican seeds.; A.P. de la Rosa, Scientist, Molecular Biology Division, Instituto Potosino de Investigacion Cientifica y Tecnologica, San Luis Potosi, S.L.P., Mexico, Research interest: bioactive components in native Mexican seeds; M.F. Leon-Galvan, Scientist, Molecular Biology Division, Instituto Potosino de Investigacion Cientifica y Tecnologica, San Luis Potosi, S.L.P., Mexico, Research interest: bioactive components in native Mexican seeds; A. De Leon-Rodriguez, Scientist, Molecular Biology Division, Instituto Potosino de Investigacion Cientifica y Tecnologica, San Luis Potosi, S.L.P., Mexico, Research interest: bioactive components in native Mexican seeds; E.G. de Mejia, Associate Professor, Dept of Food Science and Human Nutrition, University of Illinois, Champaign-Urbana, IL, USA. Research interest: Bioactive compounds in plants Jeong JH, Professor, Andong University, Korea; Park JH , Assistant Professor, Jungwan University, Korea, Lee JR, Jeong JB, Cheong YK, Graduate Students, Andong University, Korea. Research interest: Herbal medicine TARGET AUDIENCES: Biomedical researchers, plant biologists, dietitians, health professionals, nutraceutical industry, pharmaceutical industry, agronomists, plant breeders, plant geneticists, food scientists, nutritionists PROJECT MODIFICATIONS: None
Impacts
A major finding is that lunasin is bioavailable when soymilk is administered orally to men, the first studies in human. This suggests that commercially available soy products are sources of lunasin in the human diet and this information can be used to promote the larger use of lunasin to the public. The presence of lunasin in other cereals and legumes suggests that other sources of lunasin can be exploited. Our work has attracted a number of collaborators from the US and around the world including Mexico, Korea, Philippines, Italy, the European Union, University of Illinois, and University of Arkansas. The University of Bologna recently submitted a proposal with the acronym FUSION ("FUture in health: new conceptS of functional quality for the preventION of chronic and degenerative pathologies in European countries" to the 7th Framework-KBBE collaborative projects for evaluation by the European Commission. The project will deal with bioactive peptides from cereal and pseudo-cereal sources and development of functional bakery products bearing health claims for the prevention of cardiovascular diseases. The consortium is formed by 23 partners (10 academic institutions and 13 small medium enterprises), from 11 EU countries. A clinical trial on the use of lunasin for cervical cancer prevention and therapy in the Philippines has been proposed.
Publications
- 1.Jeong HJ , Jeong JB, Kim DS, Park JH, Lee JB, Kweon DH, Chung GY, Seo EW, and de Lumen BO. The cancer preventive peptide lunasin from wheat is bioavailable and inhibits core histone acetylation. Cancer Letters 255: 42-48 (2007) PMID: 17481808
- 2. Park JH, Jeong HJ, de Lumen BO. In vitro digestibility of the cancer-preventive soy peptides lunasin and BBI. J Agric Food Chem.55:10703-6 (2007). PMID: 18038984
- 3. Jeong JB, Jeong HJ, Park JH, Lee SH, Lee JR, Lee HK, Chung GY, Choi JD, de Lumen BO. Cancer preventive peptide lunasin from Solanum nigrum L. inhibits acetylation of core histones H3 and H4 and phosphorylation of retinoblastoma protein (Rb). J Agric Food Chem. 55(26):10707-13 (2007). PMID: 18038993
- 4. Park JH, Jeong JB, de Lumen BO, Jeong HJ. The anticancer properties of lunasin from aged callus induced by the soybean tissue culture. Korean J Plant Res 20: 518-23 (2007)
- 25. Jeong HJ, Jeong, JB, Hsieh CC, de Lumen, BO. 2010 Lunasin is prevalent in Barley, is bioavailable and bioactive in in vivo and in vitro studies. Nutrition and Cancer 2010 No;62(8):1113-9 PMID 21058199
- 26. Hernandez-Ledesma B, Chien CC, de Lumen BO. 2010 Lunasin, a novel cancer preventive peptide. In Nuts and Seeds in Health and Disease Prevention (Ed. Preedy) 2010
- 5. Silva-Sanchez C, Barba de la Rosa AP, Leon-Galvan MF, de Lumen BO, de Leon-Rodriguez A, de Mejia EG. Bioactive Peptides in Amaranth (Amaranthus hypochondriacus) Seed. J Agric Food Chem. 56:1233-40 (2008). PMID: 18211015
- 6. de Lumen, BO. Lunasin: A novel cancer preventive seed peptide that modifies chromatin. J AOAC International 4:932-935. (2008) PMID: 18727555
- 7. Hernandez-Ledesma B, Hsieh CC, de Lumen BO. Lunasin, a novel seed peptide for cancer prevention. Peptides 30:426-430 (2009).PMID 19056440
- 8. Park JH, Jeong JB, Lee JR, de Lumen BO, Jeong HJ. Effect of lunasin extracted from millet (Panicum miliaceum) on the activity of histone acetyltransferase yGCN5 and p/CAF. Korean J Plant Res 22: 203-208 (2009)
- 9. Dia VP, Torres S, de Lumen BO, Erdman JW, de Mejia EG. Presence of lunasin in plasma of men after soy protein consumption. J Agric Food Chem. 57:1260-1266 (2009,) PMID 19199603
- 10. Hernandez-Ledesma, B, de Lumen, BO. Lunasin: A novel cancer preventive seed peptide Perspectives in Medicinal Chemistry 2:75-80 (2008)
- 15. Jeong JH, Lee JR, Park JH , Jeong JB, Cheong YK , de Lumen BO. The cancer preventive seed peptide lunasin from rye is bioavailable and bioactive Nutrition and Cancer 61: 680-6 (2009)
- 16. Hernandez-Ledesma, B, Hsieh, CC, de Lumen, BO. Lunasin, a novel seed peptide for cancer prevention. Peptides 30: 426-30 (2009). Epub 2008 Nov 13. Review PMID19056440
- 17. Jeong JH, Lee JR, Park JH , Jeong JB, Cheong YK , de Lumen BO. The cancer preventive lunasin from rye is bioavailable and bioactive. Nutr Cancer 61: 680-6 (2009) PMID 19638942
- 18. Ledesma-Hernandez B, Hsieh CC, de Lumen, BO. 2009 Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasin in RAW 264.7 macrophages. Biochem Biophys Res Commun 390: 803-8. Epub 2009 Oct 15 PMID19836349
- 19. Hernandez-Ledesma B, Hsieh CC, de Lumen BO. 2009 Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasin in RAW 264.7 macrophages. Biochem Biophys Res Commun 2009 Dec 18;390:803-8. E pub 2009 Oct 15.
- 20. Jeong JB, de Lumen BO, Jeong HJ. 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 Lett 2010 Jul 1; 293:58-64. Epub 2010 Jan 18 PMID: 20083341
- 21. Hsieh CC, Hernandez-Ledesma B, de Lumen BO. 2010 Lunasin, a novel seed peptide, snsitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact2010 Jul 30: 186:127-34. Epub May 21 PMID: 20457246
- 22. Hsieh CC, Hernandez-Ledesma B, Jeong HJ, Park JH, de Lumen BO. 2010 Complementary roles in cancer prevention: protease inhibitor makes the cancer preventive peptide lunasin bioavailable. PLoS One. 2010 Jan 26;5(1):e8890. PubMed PMID: 20126654; PubMed Central PMCID: PMC2811193.
- 11. Dia VP, Wang W, Oh VL, de Lumen BO, de Mejia EG. Isolation, purification and characterization of lunasin from defatted soyeban flour and in vitro evaluation of its anti-inflammatory activity. Food Chemistry (in press, 2009)
- 12. Hernandez-Ledesma, B, de Lumen, BO. Lunasin. Encyclopedia of Cancer (2008)
- 13. Hernandez-Ledesma, B, de Lumen, BO. Nutraceuticals Encyclopedia of Cancer (2008) . 14. de Lumen BO. Lunasin, a novel cancer preventive peptide that modifies chromatin.J AOAC Int 91:932-5 (2008)
- 23. Maldonado-Cervantes E., Jeong HJ, Leon-Galvan F, Barrera-Pacheco A, De Leon-Rodriguez A, Gonzalez de Mejia E, de Lumen BO, Barba de la Rosa AP, 2010. Amaranth lunasin-like peptide internalizes into the cell nucleus and inhibits chemical carcinogen-induced transformation of NIH 3T3 cells. Peptides 2010 Jun 25 [Epub a head of print] PMID: 20599579
- 24. Chien CC, Hernandez-Ledesma B, de Lumen BO. 2010 Soybean Peptide Lunasin Suppresses in vitro and in vivo 7,12-Dimethylbenz[a]anthracene-Induced Tumorigenesis. J Food Science (in press)
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Progress 01/01/08 to 12/31/08
Outputs
OUTPUTS: In collaboration with our colleagues at San Luis Potosi, Mexico, the lunasin in amaranth was characterized. Amaranth seeds are considered the "Golden Grain" of the Aztecs because of their health benefits. This is the first study that reports the presence of a lunasin-like peptide and other potentially bioactive peptides in amaranth. This confirms the healthful benefits of consuming amaranth. PARTICIPANTS: C. Silva-Sanchez, Scientist, Molecular Biology Division, Instituto Potosino de Investigacion Cientifica y Tecnologica, San Luis Potosi, S.L.P., Mexico, Research interest: bioactive components in native Mexican seeds.; A.P. de la Rosa, Scientist, Molecular Biology Division, Instituto Potosino de Investigacion Cientifica y Tecnologica, San Luis Potosi, S.L.P., Mexico, Research interest: bioactive components in native Mexican seeds; M.F. Leon-Galvan, Scientist, Molecular Biology Division, Instituto Potosino de Investigacion Cientifica y Tecnologica, San Luis Potosi, S.L.P., Mexico, Research interest: bioactive components in native Mexican seeds; A. De Leon-Rodriguez, Scientist, Molecular Biology Division, Instituto Potosino de Investigacion Cientifica y Tecnologica, San Luis Potosi, S.L.P., Mexico, Research interest: bioactive components in native Mexican seeds; E.G. de Mejia, Associate Professor, Dept of Food Science and Human Nutrition, University of Illinois, Champaign-Urbana, IL, USA. Research interest: Bioactive compounds in plants TARGET AUDIENCES: Biomedical researchers, plant biologists, dietitians, health professionals, nutraceutical industry, pharmaceutical industry, agronomists, plant breeders, plant geneticists, food scientists, nutritionists PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
We report for the first time the presence and characterization of the cancer preventive lunasin in amaranth seeds. Amaranth is called the "Golden Grain of the Aztecs" because it is rich in protein with high nutritional value. Besides lunasin, this is also the first report on other potentially bioactive peptides in amaranth protein fractions. This confirms the health benefits of amaranth and could lead to a more widespread consumption of this grain beyond the Aztec community in Mexico and South America. Amaranth is already incorporated in certain breakfast cereals in the US. I also published a review on lunasin in the journal of the American Organization of Analytical Chemists.
Publications
- Silva-Sanchez, C., Barba de la Rosa, A.P., Leon-Galvan, M.F., de Lumen, B.O., de Leon-Rodriguez, A. and de Mejia, E.G. 2008. Bioactive peptides in amaranth (Amaranthus hypochondriacus) seed. J. Agric. Food Chem. 56:1233-1240. PMID: 18211015
- de Lumen, B.O. 2008. Lunasin: a novel cancer preventive seed peptide that modifies chromatin. J. A.O.A.C. International 4:932-935. PMID: 18727555
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Progress 01/01/07 to 12/31/07
Outputs
OUTPUTS: Soybean lunasin is characterized by mass peptide mapping, partial purification, and measurement of bioactivities of the various purified fractions and protein expression in the developing seed. BBI, a soy protease inhibitor, protects lunasin from digestion when soy protein is consumed orally. Lunasin from wheat, a new source of the peptide, is bioavailable and bioactive. Lunasin extracted from wheat and from the livers of rats fed with lunasin-enriched wheat (LEW) inhibit acetylation of core histone H3- and H4. Lunasin from Solanum nigrum L. (SNL), a plant indigenous to northeast Asia used as herbal medicine is bioavailable and bioactive. Presentations: 1) "Iwasan and Kanser: Lunasin, a Cancer Preventive Seed Peptide", Severino and Paz Koh Lecture Award, 2/16/07, 27th Annual Meeting of Philippine American Academy of Science and Engineering, Manila, Philippines. 2) "Lunasin, a Cancer Preventive Seed Peptide", College of Natural Resources Research Showcase, 3/1/07. 3) "Cancer
Preventive Peptide Lunasin from Wheat Inhibits Histone Acetylation", 2007 Annual Meeting, American Association for Cancer Research, Los Angeles, CA, 4/14-18/07. 4) "Lunasin, a Cancer Preventive Seed Peptide That Modifies Chromatin", Dept of Food Science and Human Nutrition, Urbana, IL (delivered as part of Visiting Professorship at UIUC May-June, 2007), 6/8/07.5) "Lunasin, a Cancer Preventive Seed Peptide That Modifies Chromatin", Gyeung Bok Bioindustry Institute, Andong University, Andong, Korea, 6/29/07. 6) "Natural Complementary Roles in Cancer Prevention", IMPACT (Innovative Minds in Prostate Cancer Today, Atlanta, GA, 9/7/07. 7) "Lunasin: A Novel Cancer Preventive Seed Peptide", Arkansas Children Nutrition Center, University of Arkansas, Little Rock, AK, 9/20/07. 8) "Lunasin: A Novel Cancer Preventive Seed Peptide", Invited Oral Presentation 121st AOAC International Annual Meeting. Session "Accurate Analysis of Amino Acids and Bioactive Peptides in Foods and Dietary Supplements",
Anaheim, CA, 9/16-20/07. 9) "Lunasin: A Novel Cancer Preventive Seed Peptide", NS&T 293 Presentation to new graduate students, Nutritional Sciences and Toxicology, UC Berkeley, 10/3/07. 10) "Lunasin: A Novel Cancer Preventive Seed Peptide", CB 294, Comparative Biochemistry Graduate Seminar, Nutritional Sciences and Toxicology, UC Berkeley, 10/9/07.11) "Lunasin: A Novel Cancer Preventive Seed Peptide", Marine Sciences Institute, University of the Philippines, Diliman, Metro Manila, 12/5/07. Patents: 1) de Lumen, B.O. and A.F. Galvez. Soybean Protein Nutraceuticals, Australian Patent No. 762977 (Oct 23, 2003). 2) de Lumen BO, Galvez AF. LUNASIN PEPTIDES. European Patent Office Patent No.: 1017798 issued 05/04/2005. 3) de Lumen BO, Galvez AF. LUNASIN PEPTIDES Australia Patent No.: 731631 issued 07/19/2001. 4) de Lumen BO, Galvez AF. LUNASIN PEPTIDES Canada Patent No.: 2,303,061 issued 05/04/2005. 5) de Lumen BO, Galvez AF. LUNASIN PEPTIDES Denmark Patent No.: 1017798 issued 11/27/2007.
PARTICIPANTS: Hyung Jin Jeong, PhD, Professor, School of Bioresources science, Andong National University, Andong, Korea, Research interest: Cancer prevention. Jin Boo Jeong, MS, Graduate student (PhD course), School of Bioresources Science, Andong National University, Andong, Korea, Research interest: Cancer prevention. Dae Seop Kim, MS, Researcher, School of Bioresources Science, Andong National University, Andong, Korea, Research interest: Cancer prevention. Jae Ho Park, PhD, Research Professor, School of Bioresources Science, Andong National University, Andong, Korea, Research interest: Cancer prevention. Jung Bok Lee, PhD, Chief Researcher, HansBio, 101 Research Building, Gyengbuk Institute for Bio Industry, Andong, Korea, Research interest: Highly advanced natural substances by a microorganism. Dae Hyuk Kweon, PhD, Professor, Department of Genetic Engineering, Sungkyunkwan University, Suwon, Korea, Research interest: Protein chemistry, electron paramagnetic resonance,
endocytosis. Gyu Young Chung, PhD, Professor, School of Bioresources Science, Andong National University, Andong, Korea, Research interest: Plant taxonomy. Eul Won Seo, PhD, Professor, College of Natural Science, Andong National University, Andong, Korea, Research interest: Animal physiology. Sun Hee Lee, MS, Assistant Teacher, College of Natural Science, Andong National University, Andong, Korea, Research interest: Plant taxonomy. Jeong Rak Lee, BS, Graduate student (MS course), School of Bioresources Science, Andong National University, Andong, Korea, Research interest: Cancer prevention. Hee Kyeong Lee, BS, Graduate student (MS course), School of Bioresources Science, Andong National University, Andong, Korea, Research interest: Cancer prevention. Jeong Doo Choi, PhD, Chief Researcher, Institute for Bioindustry, Andong, Korea, Research interest: Functional food and herbal medicine.
TARGET AUDIENCES: Biomedical researchers, plant biologists, dietitians, health professionals, nutraceutical industry, pharmaceutical industry, agronomists, plant breeders, plant geneticists, food scientists, nutritionists
Impacts
We report for the first time, the following: 1) Extensive characterization of lunasin in soy. 2) Protease inhibitors in soy such as Bowman Birk Inhibitor (BBI) and Kunitz trypsin inhibitor (KTI) protect lunasin from digestion. 3) Lunasin in wheat is bioavailable and bioactive. 4) Lunasin in Solanum nigrum, a medicinal plant from Northeast Asia, is bioavailable and bioactive. 5) Lunasin is showing a general pattern of being present in "healthy grains". The presence of lunasin in seed crops other than soy and which are considered "healthy", adds to the evidence that consumption of plant foods is healthy and reduces the risk of cancer. Although soy is well studied in this respect, the discovery of lunasin in cereal crops points to the significance of cereals in contributing to reducing the risks of cancer. 6) The patents granted would allow the commercialization of lunasin technology.
Publications
- Jeong, H.J., Jeong, J.B., Kim, D.S. and de Lumen, B.O. 2007. Inhibition of core histone acetylation by the cancer preventive peptide lunasin. J. Agric. Food Chem. 55:632-637.
- Jeong, H.J., Jeong, J.B., Kim, D.S., Park, J.H., Lee, J.B., Kweon, D.H., Chung, G.Y., Seo, E.W. and de Lumen, B.O. 2007. The cancer preventive peptide lunasin from wheat is bioavailable and inhibits core histone acetylation. Cancer Letters 255:42-48.
- Park, J.H., Jeong, H.J. and de Lumen, B.O. 2007. In vitro digestibility of the cancer-preventive soy peptides lunasin and BBI. J. Agric. Food Chem. 55:10703-10706.
- Jeong, J.B., Jeong, H.J., Park, J.H., Lee, S.H., Lee, J.R., Lee, H.K., Chung, G.Y., Choi, J.D. and de Lumen, B.O. 2007. Cancer preventive peptide lunasin from Solanum nigrum L. inhibits acetylation of core histones H3 and H4 and phosphorylation of retinoblastoma protein (Rb). J. Agric. Food Chem. 55:10707-10713.
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