Benito O. de LumenProfessor Ph.D. (Agricultural Chemistry/Biochemistry), University of California, Davis, 1971 (510) 642-8144 |
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Lunasin: a Cancer Preventive Peptide in Seeds
Epidemiological data supporting the link between consumption of plant foods and reduced incidence of cancer have led to studies on bioactive components such as phytoestrogens and protease inhibitors. In 2001, we reported for the first time the cancer preventive properties of a unique peptide in soy that we termed lunasin (from the Pilipino word lunas for cure), demonstrating its efficacy in mammalian cells and in a skin cancer mouse model against chemical carcinogens and oncogenes.
Lunasin is 43-amino acid peptide with 8 aspartic acid (D) in the carboxyl end, preceded by a cell adhesion motif RGD and a predicted helical region with structural homology to chromatin binding proteins. The first indication that lunasin has profound biological effects was when constitutive expression of the lunasin cDNA in E. coli and in mammalian cells led to mitotic arrest and eventually cell death, affecting both non-tumorigenic and cancer cells. Thus, while the exogenous addition of lunasin peptide in the presence of carcinogens prevents carcinogenesis, the constitutive expression of the lunasin gene in mammalian cells leads to cell death suggesting that the lunasin gene could be used for cancer therapy when coupled with a delivery system that targets cancer cells selectively.
Lunasin has now been found in barley, wheat, Solanum family, amaranth (the golden grain of the Aztecs in South and Central America) and rye. These seeds are considered "healthy" and our findings serve to link seed consumption and reduced incidence of cancer. We are carrying out animal experiments to demonstrate further the efficacy of diet-administered lunasin against breast, prostate and colon cancer.
We are also elucidating the molecular mechanisms by which lunasin disrupts carcinogenesis. Lunasin peptide has the unique ability of internalizing into mammalian cells when added exogenously and eventually localizing in the nucleus. The peptide inhibits histone acetylation and we are confirming that it also inhibits retinoblastoma phosphorylation. We continue to elucidate how these biochemical properties of lunasin could play major roles in disrupting carcinogenesis.
Representative Publications
1: Silva-Sánchez C, de la Rosa AP, León-Galván MF, de Lumen BO, de León-Rodríguez A, de Mejía EG. Bioactive peptides in amaranth (Amaranthus hypochondriacus) seed. J Agric Food Chem. 2008 Feb 27;56(4):1233-40. Epub 2008 Jan 23. PMID: 18211015 [PubMed - indexed for MEDLINE]
2: 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. 2007 Dec 26;55(26):10707-13. Epub 2007 Nov 27. PMID: 18038993 [PubMed - indexed for MEDLINE]
3: Park JH, Jeong HJ, Lumen BO. In vitro digestibility of the cancer-preventive soy peptides lunasin and BBI. J Agric Food Chem. 2007 Dec 26;55(26):10703-6. Epub 2007 Nov 27. PMID: 18038984 [PubMed - indexed for MEDLINE]
4: Jeong HJ, Jeong JB, Kim DS, Park JH, Lee JB, Kweon DH, Chung GY, Seo EW, de Lumen BO. The cancer preventive peptide lunasin from wheat inhibits core histone acetylation. Cancer Lett. 2007 Sep 18;255(1):42-8. Epub 2007 May 3. PMID: 17481808 [PubMed - indexed for MEDLINE]
5: Jeong HJ, Jeong JB, Kim DS, de Lumen BO. Inhibition of core histone acetylation by the cancer preventive peptide lunasin. J Agric Food Chem. 2007 Feb 7;55(3):632-7. PMID: 17263453 [PubMed - indexed for MEDLINE]
6: Park JH, Jeong HJ, de Lumen BO. Contents and bioactivities of lunasin, bowman-birk inhibitor, and isoflavones in soybean seed. J Agric Food Chem. 2005 Oct 5;53(20):7686-90. PMID: 16190617 [PubMed - indexed for MEDLINE]
7: de Lumen BO. Lunasin: a cancer-preventive soy peptide. Nutr Rev. 2005 Jan; 63(1):16-21. Review. PMID: 15730231 [PubMed - indexed for MEDLINE]
8: Gonzalez de Mejia E, Vásconez M, de Lumen BO, Nelson R. Lunasin concentration in different soybean genotypes, commercial soy protein, and isoflavone products. J Agric Food Chem. 2004 Sep 22;52(19):5882-7. PMID: 15366837 [PubMed - indexed for MEDLINE]
9: Hsieh EA, Chai CM, de Lumen BO, Neese RA, Hellerstein MK. Dynamics of keratinocytes in vivo using HO labeling: a sensitive marker of epidermal proliferation state. J Invest Dermatol. 2004 Sep;123(3):530-6. PMID: 15304093 [PubMed - indexed for MEDLINE]
10: Lam Y, Galvez A, de Lumen BO. Lunasin suppresses E1A-mediated transformation of mammalian cells but does not inhibit growth of immortalized and established cancer cell lines. Nutr Cancer. 2003;47(1):88-94. PMID: 14769542 [PubMed - indexed for MEDLINE]
11: Jeong HJ, Park JH, Lam Y, de Lumen BO. Characterization of lunasin isolated from soybean. J Agric Food Chem. 2003 Dec 31;51(27):7901-6. PMID: 14690371 [PubMed - indexed for MEDLINE]
12: Jeong HJ, Lam Y, de Lumen BO. Barley lunasin suppresses ras-induced colony formation and inhibits core histone acetylation in mammalian cells. J Agric Food Chem. 2002 Oct 9;50(21):5903-8. PMID: 12358457 [PubMed - indexed for MEDLINE]
13: Galvez AF, Chen N, Macasieb J, de Lumen BO. Chemopreventive property of a soybean peptide (lunasin) that binds to deacetylated histones and inhibits acetylation. Cancer Res. 2001 Oct 15;61(20):7473-8. PMID: 11606382 [PubMed - indexed for MEDLINE]
14: Galvez AF, de Lumen BO. A soybean cDNA encoding a chromatin-binding peptide inhibits mitosis of mammalian cells. Nat Biotechnol. 1999 May;17(5):495-500. PMID: 10331812 [PubMed - indexed for MEDLINE]