Lunasin and Cancer – worth doing your homework

Lunasin and Cancer – worth doing your homework

Dr. Weeks’ Comment:   Lunasin  is an anti-cancer peptide derived from soy which has solid science behind it.   Many patients seek immune enhancing agents which also kill cancer. Sadly, most oncologists are unaware of lunasin so this summary may be helpful for those addressing cancer.  Lunasin is available from SAFALAB  by calling 360-341-2303. 

“… Lunasin is a peptide derived from the soybean 2S albumin seed protein that has both anticancer and anti-inflammatory activities…”

 

1.
Exp Biol Med (Maywood). 2014 May 1;239(5):519-28. doi: 10.1177/1535370214522180. Epub 2014 Mar 13.

Understanding Lunasin‘s biology and potential as a cancer therapeutic by utilizing Drosophila genetics.

Abstract

Soy contains many bioactive molecules known to elicit anticancer effects. One such peptide, Lunasin, has been shown to selectively act on newly transformed cells while having no cytotoxic effect on non-tumorigenic or established cancer cell lines. While this effect on in vitro systems is promising, Lunasin‘s efficacy in an in vivo system is yet to be assessed. In this review, we discuss the state of knowledge with respect to Lunasinand then review some of the powerful genetic tools available in Drosophila. The availability of a sophisticated genetic tool box makes Drosophila an excellent genetic model well suited to studying the biology of Lunasinand its effect on tumor progression in an in vivo model organism.

KEYWORDS:

Drosophila; Lunasincancer; metastasis; tumors

PMID:

 

24625440

 

[PubMed – in process]
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2.
Cancer Immunol Immunother. 2014 Mar;63(3):283-95. doi: 10.1007/s00262-013-1513-8. Epub 2013 Dec 22.

Soypeptide lunasin in cytokine immunotherapy for lymphoma.

Abstract

Immunostimulatory cytokines can enhance anti-tumor immunity and are part of the therapeutic armamentarium for cancer treatment. We have previously reported that post-transplant lymphoma patients have an acquired deficiency of signal transducer and activator of transcription 4, which results in defective IFNγ production during clinical immunotherapy. With the goal of further improving cytokine-based immunotherapy, we examined the effects of a soybean peptide called lunasin that synergistically works with cytokines on natural killer (NK) cells. Peripheral blood mononuclear cells of healthy donors and post-transplant lymphoma patients were stimulated with or without lunasin in the presence of IL-12 or IL-2. NK activation was evaluated, and its tumoricidal activity was assessed using in vitro and in vivo tumor models. Chromatin immunoprecipitation assay was performed to evaluate the histone modification of gene loci that are regulated by lunasin and cytokine. Adding lunasin to IL-12- or IL-2-stimulated NK cells demonstrated synergistic effects in the induction of IFNG and GZMB involved in cytotoxicity. The combination of lunasin and cytokines (IL-12 plus IL-2) was capable of restoring IFNγ production by NK cells from post-transplant lymphoma patients. In addition, NK cells stimulated with lunasin plus cytokines displayed higher tumoricidal activity than those stimulated with cytokines alone using in vitro and in vivo tumor models. The underlying mechanism responsible for the effects of lunasinon NK cells is likely due to epigenetic modulation on target gene loci. Lunasin represents a different class of immune modulating agent that may augment the therapeutic responses mediated by cytokine-based immunotherapy.

PMID:

 

24363024

 

[PubMed – indexed for MEDLINE] 
PMCID:

 

PMC3928510

 

Free PMC Article

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3.
Cancer Epidemiol. 2013 Dec;37(6):1014-9. doi: 10.1016/j.canep.2013.09.013. Epub 2013 Oct 21.

Eukaryotic expression vectors containing genes encoding plant proteins for killing of cancer cells.

Abstract

BACKGROUND:

Gene therapy has attracted attention for its potential to specifically and efficiently targetcancer cells with minimal toxicity to normal cells. At present, it offers a promising direction for the treatment ofcancer patients. Numerous vectors have been engineered for the sole purpose of killing cancer cells, and some have successfully suppressed malignant tumours. Many plant proteins have anticancer properties; consequently, genes encoding some of these proteins are being used to design constructs for the inhibition of multiplying cancer cells. Results: Data addressing the function of vectors harbouring genes specifically encoding ricin, saporin, lunasin, linamarase, and tomato thymidine kinase 1 under the control of different promoters are summarised here. Constructs employing genes to encode cytotoxic proteins as well as constructs employing genes of enzymes that convert a nontoxic prodrug into a toxic drug are considered here.

CONCLUSION:

Generation of eukaryotic expression vectors containing genes encoding plant proteins for killing of cancer cells may permit the broadening of cancer gene therapy strategy, particularly because of the specific mode of action of anticancer plant proteins.

Copyright © 2013 Elsevier Ltd. All rights reserved.

KEYWORDS:

CancerCancer gene therapy; Cell death; Enzyme/prodrug combination; Gene expression; Plant proteins; Therapeutic genes; Toxic proteins; Toxicity

PMID:

 

24156931

 

[PubMed – in process]
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4.
Protein Pept Lett. 2013 Apr;20(4):424-32.

Chemopreventive properties of Peptide Lunasin: a review.

Abstract

Cancer has become one the most common causes of death in developed countries and has been defined as the medical challenge of our times. Accumulating evidence support the notion that prevention can be a major component of cancer control. Chemoprevention, a relatively new and promising strategy to prevent cancer, is defined as the use of natural and/or synthetic substances to block, reverse, or retard the process of carcinogenesis. Plant-based foods, containing significant amounts of bioactive phytochemicals, may provide desiderable health benefits beyond basic nutrition to reduce the process of cancer. In the last few years, proteins and peptides have become one group of nutraceuticals that show potential results in preventing the different stages of cancer including initiation, promotion, and progression. Lunasin is a 43- amino acid peptide identified in soybean and other plants whose anti-carcinogenic activity has been demonstrated both in in vitro and in vivo assays. Moreover, this peptide has been found to exert anti-inflammatory and antioxidant properties that could contribute to its chemopreventive effects. Lunasin‘s bioactivity and its molecular mechanism(s) of actions are summarized in this review.

PMID:

 

23016582

 

[PubMed – indexed for MEDLINE]
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5.
Genes Nutr. 2013 Jan;8(1):79-90. doi: 10.1007/s12263-012-0307-5. Epub 2012 Aug 3.

The soybean peptide lunasin promotes apoptosis of mammary epithelial cells via induction of tumor suppressor PTEN: similarities and distinct actions from soy isoflavone genistein.

Abstract

Breast cancer is the leading cause of cancer deaths in women. Diet and lifestyle are major contributing factors to increased breast cancer risk. While mechanisms underlying dietary protection of mammary tumor formation are increasingly elucidated, there remains a dearth of knowledge on the nature and precise actions of specific bioactive components present in foods with purported health effects. The 43-amino acid peptide lunasin (LUN) is found in soybeans, is bioavailable similar to the isoflavone genistein (GEN), and thus may mediate the beneficial effects of soy food consumption. Here, we evaluated whether LUN displays common and distinct actions from those of GEN in non-malignant (mouse HC11) and malignant (human MCF-7) mammary epithelial cells. In MCF-7 cells, LUN up-regulated tumor suppressor phosphatase and tensin homolog deleted in chromosome ten (PTEN) promoter activity, increased PTEN transcript and protein levels and enhanced nuclear PTEN localization, similar to that shown for GEN in mammary epithelial cells. LUN-induced cellular apoptosis, akin to GEN, was mediated by PTEN, but unlike that for GEN, was p53-independent. LUN promoted E-cadherin and β-catenin non-nuclear localization similar to GEN, but unlike GEN, did not influence the proliferative effects of oncogene Wnt1 on HC11 cells. Further, LUN did not recapitulate GEN inhibitory effects on expansion of the cancer stem-like/progenitor population in MCF-7 cells. Results suggest the concerted actions of GEN and LUN on cellular apoptosis for potential mammary tumor preventive effects and highlight whole food consumption rather than intake of specific dietary supplements with limited biological effects for greater health benefits.

PMID:

 

22864686

 

[PubMed] 
PMCID:

 

PMC3535001

 

Free PMC Article

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6.
PLoS One. 2012;7(4):e35409. doi: 10.1371/journal.pone.0035409. Epub 2012 Apr 13.

Scalable purification and characterization of the anticancer lunasin peptide from soybean.

Abstract

Lunasin is a peptide derived from the soybean 2S albumin seed protein that has both anticancer and anti-inflammatory activities. Large-scale animal studies and human clinical trials to determine the efficacy oflunasin in vivo have been hampered by the cost of synthetic lunasin and the lack of a method for obtaining gram quantities of highly purified lunasin from plant sources. The goal of this study was to develop a large-scale method to generate highly purified lunasin from defatted soy flour. A scalable method was developed that utilizes the sequential application of anion-exchange chromatography, ultrafiltration, and reversed-phase chromatography. This method generates lunasin preparations of >99% purity with a yield of 442 mg/kg defatted soy flour. Mass spectrometry of the purified lunasin revealed that the peptide is 44 amino acids in length and represents the original published sequence of lunasin with an additional C-terminal asparagine residue. Histone-binding assays demonstrated that the biological activity of the purified lunasin was similar to that of synthetic lunasin. This study provides a robust method for purifying commercial-scale quantities of biologically-active lunasin and clearly identifies the predominant form of lunasin in soy flour. This method will greatly facilitate the development of lunasin as a potential nutraceutical or therapeutic anticancer agent.

PMID:

 

22514740

 

[PubMed – indexed for MEDLINE] 
PMCID:

 

PMC3326064

 

Free PMC Article

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7.
Nutr Cancer. 2012;64(1):111-20. doi: 10.1080/01635581.2012.630159. Epub 2011 Nov 18.

Synthesis of the cancer preventive peptide lunasin by lactic acid bacteria during sourdough fermentation.

Abstract

This study aimed to exploit the potential of sourdough lactic acid bacteria to release lunasin during fermentation of cereal and nonconventional flours. The peptidase activities of a large number of sourdough lactic acid bacteria were screened using synthetic substrates. Selected lactic acid bacteria were used as sourdough starters to ferment wholemeal wheat, soybean, barley, amaranth, and rye flours. Proteinase activity during fermentation was characterized by SDS-PAGE analysis of the water-soluble extracts. Albumins having molecular masses of 18 to 22 kDa, which included the size of lunasin precursors, were markedly affected by proteolysis of lactic acid bacteria. After fermentation, lunasin from the water-soluble extracts was quantified, purified, and identified through RP-HPLC and nano-LC-ESI-MS analyses. Compared to control doughs, the concentration of lunasin increased up to 2-4 times during fermentation. Lactobacillus curvatus SAL33 and Lactobacillus brevis AM7 synthesized the highest concentrations of lunasin in all the flours. Besides the presence of the entire lunasin sequence, fragments containing the immunoreactive epitope RGDDDDDDDDD were also found. This study shows that fermentation by lactic acid bacteria increased the concentration oflunasin to levels that would suggest new possibilities for the biological synthesis and for the formulation of functional foods.

PMID:

 

22098174

 

[PubMed – indexed for MEDLINE]
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8.
Cancer Lett. 2011 Dec 27;313(2):167-80. doi: 10.1016/j.canlet.2011.09.002. Epub 2011 Sep 10.

Lunasin potentiates the effect of oxaliplatin preventing outgrowth of colon cancermetastasis, binds to α5β1 integrin and suppresses FAK/ERK/NF-κB signaling.

Abstract

The effect of lunasin on colon cancer metastasis was studied using three human colon cancer cell lines in vitro and a liver metastasis model of colon cancer in vivo. Lunasin bound with α5β1 integrin and internalized into the nucleus of KM12L4 human colon cancer cells. Lunasin (10 μM) inhibited the activation of focal adhesion kinase (FAK) by 28%, 39% and 60% in RKO, HCT-116 and KM12L4 human colon cancer cells, respectively.Lunasin caused an increase in the expression of the inhibitor of kappa B alpha (IκB-α), a decrease in nuclear p50 NF-κB and a reduction in the migration of cancer cells. Lunasin (4 mg/kg bw) inhibited metastasis and potentiated the effect of oxaliplatin by reducing the expression of proliferating cell nuclear antigen. Liver metastatic nodules were reduced from 28 (PBS) to 14 (lunasin, P = 0.047) while combination of lunasin and oxaliplatin to 5 (P = 0.004). The tumor burden was reduced from 0.13 (PBS) to 0.10 (lunasin, P = 0.039) to 0.04 (lunasin + oxaliplatin, P < 0.0001). Moreover, lunasin potentiated the effect of oxaliplatin in modifying expression of proteins involved in apoptosis and metastasis including Bax, Bcl-2, IKK-α and p-p65. Lunasininhibited metastasis of human colon cancer cells by direct binding with α5β1 integrin suppressing FAK/ERK/NF-κB signaling, and potentiated the effect of oxaliplatin in preventing the outgrowth of metastasis.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

PMID:

 

21963225

 

[PubMed – indexed for MEDLINE]
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9.
Mol Nutr Food Res. 2011 Jul;55(7):989-98. doi: 10.1002/mnfr.201000632. Epub 2011 May 25.

Relationship between lunasin‘s sequence and its inhibitory activity of histones H3 and H4 acetylation.

Abstract

SCOPE:

Dysfunction of histone acetyltransferases (HATs) or histone deacetylases (HDACs) involved in histones acetylation has been associated with cancer. Inhibitors of these enzymes are becoming potential targets for new therapies.

METHODS AND RESULTS:

This study reports by Western-Blot analysis, that peptide lunasin is mainly an in vitro inhibitor of histone H4 acetylation by P300/cAMP-response element-binding protein (CBP)-associated factor (PCAF), with ICâ‚…â‚€ values dependent on the lysine position sensitive to be acetylated (0.83 μM (H4-Lys 8), 1.27 μM (H4-Lys 12) and 0.40 μM (H4-Lys 5, 8, 12, 16)). Lunasin is also capable of inhibiting H3 acetylation (ICâ‚…â‚€ of 5.91 μM (H3-Lys 9) and 7.81 μM (H3-Lys 9, 14)). Studies on structure-activity relationship establish that lunasin‘s sequence are essential for inhibiting H4 acetylation whereas poly-D sequence is the main active sequence responsible for H3 acetylation inhibition. Lunasin also inhibits H3 and H4 acetylation and cell proliferation (ICâ‚…â‚€ of 181 μM) in breast cancer MDA-MB-231 cells. Moreover, this peptide decreases expression of cyclins and cyclin dependent kinases-4 and -6, implicated in cell cycle pathways.

CONCLUSION:

Results from this study demonstrates lunasin‘s role as modulator of histone acetylation and protein expression that might contribute on its chemopreventive properties against breast cancer.

Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID:

 

21618425

 

[PubMed – indexed for MEDLINE]
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10.
Plant Foods Hum Nutr. 2011 Jun;66(2):107-13. doi: 10.1007/s11130-011-0229-1.

Lunasin-aspirin combination against NIH/3T3 cells transformation induced by chemical carcinogens.

Abstract

Carcinogenesis is a multistage process involving a number of molecular pathways sensitive to intervention. Chemoprevention is defined as the use of natural and/or synthetic substances to block, reverse, or retard the process of carcinogenesis. To achieve greater inhibitory effects on cancer cells, combination of two or more chemopreventive agents is commonly considered as a better preventive and/or therapeutic strategy. Lunasinis a promising cancer preventive peptide identified in soybean and other seeds. Its efficacy has been demonstrated by both in vitro and in vivo models. This peptide has been found to inhibit human breast cancerMDA-MB-231 cells proliferation, suppressing cell cycle progress and inducing cell apoptosis. Moreover,lunasin potentiates the effects on these cells of different synthetic and natural compounds, such as aspirin and anacardic acid. This study explored the role of lunasin, alone and in combination with aspirin and anacardic acid on cell proliferation and foci formation of transformed NIH/3T3 cells induced by chemical carcinogens 7,12-dimethylbenz[a]anthracene or 3-methylcholanthrene. The results revealed that lunasin, acting as a single agent, inhibits cell proliferation and foci formation. When combined with aspirin, these effects were significantly increased, indicating that this combination might be a promising strategy to prevent/treat cancer induced by chemical carcinogens.

PMID:

 

21562729

 

[PubMed – indexed for MEDLINE]
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11.
J Food Sci. 2010 Nov-Dec;75(9):H311-6. doi: 10.1111/j.1750-3841.2010.01861.x.

Soybean peptide lunasin suppresses in vitro and in vivo 7,12-dimethylbenz[a]anthracene-induced tumorigenesis.

Abstract

Lunasin is a novel peptide identified in soybean and other seeds. This study evaluated the anti-tumorigenic effects of lunasin on 7,12-dimethylbenz(a)anthracene (DMBA) and 3-methylcholanthrene-treated (MCA) fibroblast NIH/3T3 cells. Lunasin significantly inhibited cell proliferation and cancerous foci formation in these 2 chemical carcinogens-treated cells. An in vivo SENCAR mouse model induced with DMBA was used to study the mammary cancer preventive properties of dietary lunasin contained in soy protein. Tumor incidence was 67% and 50%, and the tumor generation was 1.88 ± 0.48 and 1.17 ± 0.17, respectively, for the mice fed control diet and experimental diet obtained after AIN-93G supplementation with lunasin-enriched soy protein concentrate (containing 0.23% lunasin). However, no effects were observed in mice fed AIN-93G supplemented with soy protein concentrate (containing 0.15% lunasin). The data provided illustrate the anticancer potential of lunasin both in vitro and in vivo and supports the recommendation of soy protein as a dietary component that may aid in the prevention of mammary cancer.

© 2010 Institute of Food Technologists®

PMID:

 

21535606

 

[PubMed – indexed for MEDLINE]
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12.
Nutr Cancer. 2011;63(4):623-36. doi: 10.1080/01635581.2011.539312.

Differential expression of thrombospondin (THBS1) in tumorigenic and nontumorigenic prostate epithelial cells in response to a chromatin-binding soy peptide.

Abstract

The chemopreventive properties of the chromatin-binding soy peptide, lunasin, are well documented, but its mechanism of action is unclear. To elucidate the mechanism by which lunasin reduces tumor foci formation in cultured mammalian cells, nontumorigenic (RWPE-1) and tumorigenic (RWPE-2) human prostate epithelial cells were treated with lunasin followed by gene expression profiling and characterization of the chromatin acetylation status for certain chemopreventive genes. The genes HIF1A, PRKAR1A, TOB1, and THBS1 were upregulated by lunasin in RWPE-1 but not in RWPE-2 cells. Using histone acetyltransferase (HAT) assays with acid-extracted histones as templates, we showed that lunasin specifically inhibited H4K8 acetylation while enhanced H4K16 acetylation catalyzed by HAT enzymes p300, PCAF, and HAT1A. These results suggest a novel mechanism for lunasin-dependent upregulation of gene expression. Chromatin immunoprecipitation (ChIP) revealed hypoacetylation of H4K16 in RWPE-2 cells, specifically at the 5′ end of THBS1 containing a CpG island. Moreover, bisulfite PCR (BSP) and subsequent DNA sequencing indicated that this CpG island was hypomethylated in RWPE-1 but hypermethylated in RWPE-2 cells. Histone hypoacetylation and DNA hypermethylation in the 5′ region of THBS1 may explain the inability of lunasin to upregulate this gene in RWPE-2 cells.

PMID:

 

21526452

 

[PubMed – indexed for MEDLINE] 
PMCID:

 

PMC3210036

 

Free PMC Article

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13.
Mol Nutr Food Res. 2011 Apr;55(4):623-34. doi: 10.1002/mnfr.201000419. Epub 2011 Jan 5.

Lunasin induces apoptosis and modifies the expression of genes associated with extracellular matrix and cell adhesion in human metastatic colon cancer cells.

Abstract

SCOPE:

Lunasin is an arginine-glycine-aspartic acid (RGD) cancer preventive peptide. The objective was to evaluate the potential of lunasin to induce apoptosis in human colon cancer cells and their oxaliplatin-resistant (OxR) variants, and its effect on the expression of human extracellular matrix and adhesion genes.

METHODS AND RESULTS:

Various human colon cancer cell lines which underwent metastasis were evaluated in vitro using cell flow cytometry and fluorescence microscopy. Lunasin cytotoxicity to different coloncancer cells correlated with the expression of α(5) b(1) integrin, being most potent to KM12L4 cells (IC(50) =”‰13”‰Î¼M). Lunasin arrested cell cycle at G2/M phase with concomitant increase in the expression of cyclin-dependent kinase inhibitors p21 and p27. Lunasin (5-25”‰Î¼M) activated the apoptotic mitochondrial pathway as evidenced by changes in the expressions of Bcl-2, Bax, nuclear clusterin, cytochrome c and caspase-3 in KM12L4 and KM12L4-OxR. Lunasin increased the activity of initiator caspase-9 leading to the activation of caspase-3 and also modified the expression of human extracellular matrix and adhesion genes, downregulating integrin α(5), SELE, MMP10, integrin β(2) and COL6A1 by 5.01-, 6.53-, 7.71-, 8.19- and 10.10-fold, respectively, while upregulating COL12A1 by 11.61-fold.

CONCLUSION:

Lunasin can be used in cases where resistance to chemotherapy developed.

Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID:

 

21462330

 

[PubMed – indexed for MEDLINE]
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14.
Cancer Metastasis Rev. 2010 Sep;29(3):511-28. doi: 10.1007/s10555-010-9241-4.

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

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.

PMID:

 

20714786

 

[PubMed – indexed for MEDLINE]
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15.
Chem Biol Interact. 2010 Jul 30;186(2):127-34. doi: 10.1016/j.cbi.2010.04.027. Epub 2010 May 21.

Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis.

Abstract

Breast cancer is one of the most common tumors in women of Western countries. The high aggressiveness and therapeutic resistance of estrogen-independent breast tumors have motivated the development of new strategies for prevention and/or treatment. Combinations of two or more chemopreventive agents are currently being used to achieve greater inhibitory effects on breast cancer cells. This study reveals that both aspirin andlunasin inhibit, in a dose-dependent manner, human estrogen-independent breast cancer MDA-MB-231 cell proliferation. These compounds arrest the cell cycle in the S- and G1-phases, respectively, acting synergistically to induce apoptosis. To begin elucidating the mechanism(s) of action of these compounds, different molecular targets involved in cell cycle control, apoptosis and signal transduction have been evaluated by real-time polymerase chain reaction (RT-PCR) array. The cell growth inhibitory effect of alunasin/aspirin combination is achieved, at least partially, by modulating the expression of genes encoding G1 and S-phase regulatory proteins. Lunasin/aspirin therapy exerts its potent pro-apoptotic effect is at least partially achieved through modulating the extrinsic-apoptosis dependent pathway. Synergistic down-regulatory effects were observed for ERBB2, AKT1, PIK3R1, FOS and JUN signaling genes, whose amplification has been reported as being responsible for breast cancer cell growth and resistance to apoptosis. Therefore, our results suggest that a combination of these two compounds is a promising strategy to prevent/treat breastcancer.

(c) 2010 Elsevier Ireland Ltd. All rights reserved.

PMID:

 

20457246

 

[PubMed – indexed for MEDLINE]
Icon for Elsevier Science
16.
Cancer Lett. 2010 Sep 1;295(1):44-53. doi: 10.1016/j.canlet.2010.02.010. Epub 2010 Mar 4.

Lunasin promotes apoptosis in human colon cancer cells by mitochondrial pathway activation and induction of nuclear clusterin expression.

Abstract

Lunasin is a naturally occurring peptide with arginine-glycine-aspartic acid motif associated to its reported biological activity. We aimed to determine the potential of lunasin from soybean to stimulate apoptosis in HT-29 colon cancer cells. Lunasin caused cytotoxicity to HT-29 cells and induced G2/M cell cycle arrest with simultaneous increased in p21 expression. Lunasin-induced apoptosis as evidenced by a twofold increase in the percentage of cells undergoing apoptosis, decreased Bcl-2:Bax ratio from 8.5 to 0.4, increased caspase-3 activity by 77% and increased expression of pro-apoptotic nuclear clusterin by five fold when compared to untreated cells. In conclusion, lunasin stimulated apoptosis in HT-29 cells by activating apoptotic mitochondrial pathways and inducing expression of the pro-apoptotic nuclear clusterin.

Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

PMID:

 

20206442

 

[PubMed – indexed for MEDLINE]
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17.
PLoS One. 2010 Jan 26;5(1):e8890. doi: 10.1371/journal.pone.0008890.

Complementary roles in cancer prevention: protease inhibitor makes the cancerpreventive peptide lunasin bioavailable.

Abstract

BACKGROUND:

The lower incidence of breast cancer among Asian women compared with Western countries has been partly attributed to soy in the Asian diet, leading to efforts to identify the bioactive components that are responsible. Soy Bowman Birk Inhibitor Concentrate (BBIC) is a known cancerpreventive agent now in human clinical trials.

METHODOLOGY/PRINCIPAL FINDINGS:

The objectives of this work are to establish the presence and delineate the in vitro activity of lunasin and BBI found in BBIC, and study their bioavailability after oral administration to mice and rats. We report that lunasin and BBI are the two main bioactive ingredients of BBIC based on inhibition of foci formation, lunasin being more efficacious than BBI on an equimolar basis. BBI and soy Kunitz Trypsin Inhibitor protect lunasin from in vitro digestion with pancreatin. Oral administration of (3)H-labeled lunasin with lunasin-enriched soy results in 30% of the peptide reaching target tissues in an intact and bioactive form. In a xenograft model of nude mice transplanted with human breast cancer MDA-MB-231 cells, intraperitoneal injections of lunasin, at 20 mg/kg and 4 mg/kg body weight, decrease tumor incidence by 49% and 33%, respectively, compared with the vehicle-treated group. In contrast, injection with BBI at 20 mg/kg body weight shows no effect on tumor incidence. Tumor generation is significantly reduced with the two doses of lunasin, while BBI is ineffective. Lunasin inhibits cell proliferation and induces cell death in the breast tumor sections.

CONCLUSIONS/SIGNIFICANCE:

We conclude that lunasin is actually the bioactive cancer preventive agent in BBIC, and BBI simply protects lunasin from digestion when soybean and other seed foods are eaten by humans.

PMID:

 

20126654

 

[PubMed – indexed for MEDLINE] 
PMCID:

 

PMC2811193

 

Free PMC Article

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18.
Mol Nutr Food Res. 2010 Mar;54(3):406-14. doi: 10.1002/mnfr.200900073.

Lunasin, with an arginine-glycine-aspartic acid motif, causes apoptosis to L1210 leukemia cells by activation of caspase-3.

Abstract

Lunasin is a novel chemopreventive peptide featuring a cell adhesion motif composed of arginine-glycine-aspartate (RGD) which has been associated to cytotoxicity to established cell lines. The objectives of this study were to determine the effect of lunasin on the viability of L1210 leukemia cells and to understand the underlying mechanisms involved. Pure lunasin and lunasin enriched soy flour (LES) caused cytotoxicity to L1210 leukemia cells with IC(50) of 14 and 16 microM (lunasin equivalent), respectively. Simulated gastrointestinal digestion showed that 25% of the original amount of lunasin survived 3 h of pepsin digestion and 3% of lunasin remained after sequential pepsin-pancreatin digestion for a total of 6 h. Cell cycle analysis showed that lunasin caused a dose-dependent G2 cell cycle arrest and apoptosis. Treatment of L1210 leukemia cells with 1 mg/mL of LES for 18 h led to an increase in the amount of apoptotic cells from 2 to 40%. Compared to untreated cells, treatment with 1 mg/mL LES showed a 6-fold increase on the expressions of caspases-8 and -9, and and a 12-fold increase on the expression of caspase-3. These results showed for the first time that lunasin, a naturally occurring peptide containing an RGD motif, caused apoptosis to L1210 leukemia cells through caspase-3 activation.

PMID:

 

19937853

 

[PubMed – indexed for MEDLINE]
Icon for John Wiley & Sons, Inc.
19.
Nutr Cancer. 2009;61(5):680-6. doi: 10.1080/01635580902850082.

The cancer preventive seed peptide lunasin from rye is bioavailable and bioactive.

Abstract

Lunasin is a unique 43-amino acid peptide that has been shown to be chemopreventive in mammalian cells and in a skin cancer mouse model against oncogenes and chemical carcinogens. In search for new sources oflunasin and to better understand the role of cereals in cancer prevention, we report here the properties oflunasin from rye. The stability and bioavailability were measured by in vitro digestibility assay using pepsin and pancreatin and feeding rats with lunasin-enriched rye (LER). Inhibition of histone acetyl transferase (HAT) and nuclear localization in mammalian cells were used to measure lunasin bioactivity. Lunasin is present in 15 out of 21 cultivars of rye analyzed. Lunasin present in rye crude protein preparation is stable to pepsin and pancreatin in in vitro digestion. The liver, kidney, and blood of rats fed LER show the presence of lunasin in Western blot. Lunasin extracted from these tissues inhibits the activities of HATs, confirming that the peptide is intact and bioactive. Lunasin purified from rye internalizes in the nuclei of mouse fibroblast cells. We conclude that lunasin in rye is bioavailable and bioactive and that consumption of rye may play an important role ofcancer prevention in rye-consuming populations.

PMID:

 

19838942

 

[PubMed – indexed for MEDLINE]
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20.
Biochem Biophys Res Commun. 2009 Dec 18;390(3):803-8. doi: 10.1016/j.bbrc.2009.10.053. Epub 2009 Oct 15.

Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasinin RAW 264.7 macrophages.

Abstract

Oxidative stress and inflammation are two of the most critical factors implicated in carcinogenesis and other degenerative disorders. We have investigated how lunasin, a known anti-cancer seed peptide, affect these factors. This peptide inhibits linoleic acid oxidation and acts as 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenger. Furthermore, using LPS-stimulated RAW 264.7 macrophages, we have demonstrated that lunasin reduces, in a significant dose-dependent manner, the production of reactive oxygen species (ROS) by LPS-induced macrophages. Lunasin also inhibits the release of pro-inflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha] and interleukine-6 [IL-6]). On the basis of these potent antioxidant and anti-inflammatory properties, we propose lunasin not only as a cancerpreventive and therapeutic agent but also as an agent against other inflammatory-related disorders.

PMID:

 

19836349

 

[PubMed – indexed for MEDLINE]
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21.
Peptides. 2009 Dec;30(12):2388-98. doi: 10.1016/j.peptides.2009.08.005. Epub 2009 Aug 12.

Lunasin and lunasin-like peptides inhibit inflammation through suppression of NF-kappaB pathway in the macrophage.

Abstract

Inflammation is part of the host defense mechanism against harmful matters and injury; however, aberrant inflammation is associated to the development of chronic diseases such as cancerLunasin is a novel peptide that demonstrates potential anticancer activity against mammalian cancer cell lines and may play a role in inflammation. The objective of this study was to determine the mechanism of action by which lunasin andlunasin-like peptides exert their anti-inflammatory properties using RAW 264.7 macrophage cell line as an in vitro model. We purified three peptides (5, 8, and 14 kDa) from defatted soybean flour with a positive immunoreactivity towards lunasin mouse monoclonal antibody. Treatment with these peptides (10-50 microM) resulted in the inhibition of pro-inflammatory markers in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. The 5 kDa peptide inhibited most potently pro-inflammatory markers including interleukin-6 production (IC(50)=2 microM), interleukin-1beta production (IC(50)=13 microM), nuclear factor-kappa B (NF-kappaB) transactivation (IC(50)=21 microM), cyclooxygenase-2 expression (IC(50)=25 microM), nitric oxide production (IC(50)=28 microM), inducible nitric oxide synthase expression (IC(50)=37 microM), prostaglandin E(2) production (IC(50)=41 microM), p65 nuclear translocation (IC(50)=48 microM) and p50 nuclear translocation (IC(50)=77 microM). In conclusion, lunasin and lunasin-like peptides purified from defatted soybean flour inhibited inflammation in LPS-induced RAW 264.7 macrophage by suppressing NF-kappaB pathway.

PMID:

 

19682518

 

[PubMed – indexed for MEDLINE]
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22.
Peptides. 2009 Feb;30(2):426-30. doi: 10.1016/j.peptides.2008.11.002. Epub 2008 Nov 13.

Lunasin, a novel seed peptide for cancer prevention.

Abstract

Carcinogenesis is a multistage process derived from a combination of multiple heritable and environmental factors. It has been reported that populations consuming high levels of soybean products have both lowercancer incidence and mortality rates in the western countries. Lunasin is a novel and promising peptide initially discovered in soy and now found in wheat, barley and other seeds. Its cancer-preventive efficacy has been shown in mammalian cells which were induced by chemical carcinogens and viral oncogenes. Moreover, this peptide has been found to prevent skin cancer in a mouse cancer model induced by chemical carcinogens. Its bioavailability after oral administration makes it a perfect candidate as a chemopreventive agent. The purpose of this article is to review the discovery of this seed peptide and the most recent evidence on its possible benefits as an anticancer agent.

PMID:

 

19056440

 

[PubMed – indexed for MEDLINE]
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23.
J AOAC Int. 2008 Jul-Aug;91(4):932-5.

Lunasin: a novel cancer preventive seed peptide that modifies chromatin.

Abstract

Lunasin is a novel cancer preventive peptide whose efficacy against chemical carcinogens and oncogenes has been demonstrated in mammalian cells and a skin cancer mouse model. In contrast, constitutive expression of the lunasin gene in mammalian cells leads to arrest of cell division and cell death. Isolated and characterized in soy, lunasin peptide is also documented in barley and wheat and is predicted to be present in many more seeds because of its possible role in seed development. Initial studies show that lunasin is bioavailable in mice when orally ingested. Lunasin internalizes into mammalian cells within minutes of exogenous application, and localizes in the nucleus after 18 h. It inhibits acetylation of core histones in mammalian cells but does not affect the growth rate of normal and established cancer cell lines. An epigenetic mechanism of action is proposed whereby lunasin selectively kills cells being transformed or newly transformed cells by binding to deacetylated core histones exposed by the transformation event, disrupting the dynamics of histone acetylation-deacetylation.

PMID:

 

18727555

 

[PubMed]
24.
Mol Nutr Food Res. 2008 Oct;52(10):1121-9. doi: 10.1002/mnfr.200700296.

Reduced mammary tumor progression in a transgenic mouse model fed an isoflavone-poor soy protein concentrate.

Abstract

Dietary exposure to soy has been associated with reduced breast cancer incidence. Soy isoflavones and protein components, such as protease inhibitors and the lunasin peptide, have been indicated as potential agents reducing carcinogenesis. In this study, the effect of soy-based diets was evaluated in a transgenic mouse model of breast carcinoma, overexpressing the neu oncogene. Neu female mice were fed for 20 wk a soy- and isoflavone-free diet (IFD), 4RF21 laboratory mouse diet, soy-based, thus isoflavone-rich (STD), or AIN-76-based semisynthetic diets with a soy protein isolate (SPI) or an isoflavone-poor soy protein concentrate (IPSP) as protein source. Mice were then sacrificed and tumors removed. Mammary tumor weights were not different in SPI versus IFD and STD fed mice. In contrast, mice fed IPSP showed reduced tumor progression versus IFD and STD groups (p < 0.05). Moreover, IPSP fed mice showed lower bromo-2′-deoxyuridine (BrdU) incorporation into breast tumor cells compared to STD and SPI fed animals (p < 0.02). Lung metastases were detected in 80% of IFD fed mice, in 70% of mice fed STD and SPI, and only in 50% of the IPSP fed animals. These results indicate that a diet containing an isoflavone-poor soy protein concentrate may inhibit breast tumor progression and metastasis development.

PMID:

 

18655005

 

[PubMed – indexed for MEDLINE]
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25.
J Agric Food Chem. 2008 Jun 11;56(11):4012-20. doi: 10.1021/jf8002009. Epub 2008 May 13.

beta-Conglycinins among sources of bioactives in hydrolysates of different soybean varieties that inhibit leukemia cells in vitro.

Abstract

Soybean is a complex matrix containing several potentially bioactive components. The objective was to develop a statistical model to predict the in vitro anticancer potential of soybean varieties based on the correlation between protein composition and bioactive components after simulated gastrointestinal enzyme digestion with their effect on leukemia mouse cells. The IC 50 values of the hydrolysates of soy genotypes (NB1-NB7) on L1210 leukemia cells ranged from 3.5 to 6.2 mg/mL. Depending on genotype, each gram of soy hydrolysates contained 2.7-6.6 micromol of total daidzein, 3.0-4.7 micromol of total genistein, 0.5-1.3 micromol of glycitein, 2.1-2.8 micromol of total saponins, 0.1-0.2 micromol of lunasin, and 0.1-0.6 micromol of Bowman-Birk inhibitor (BBI). The IC 50 values calculated from a partial least-squares (PLS) analysis model correlated well with experimental data ( R (2) = 0.99). Isoflavones and beta-conglycinin positively contributed to the cytotoxicity of soy on L1210 leukemia cells. Lunasin and BBI were potent L1210 cell inhibitors (IC 50 = 13.9 and 22.5 microM, respectively), but made modest contributions to the activity of defatted soy flour hydrolysates due to their relatively low concentrations. In conclusion, the data demonstrated that beta-conglycinins are among the major protein components that inhibit leukemia cell growth in vitro. Furthermore, it was feasible to differentiate soybean varieties on the basis of the biological effect of their components using a statistical model and a cell-based assay.

PMID:

 

18473471

 

[PubMed – indexed for MEDLINE]
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26.
Perspect Medicin Chem. 2008 Mar 25;2:75-80.

Lunasin: a novel cancer preventive seed Peptide.

Abstract

Cancer is one of the leading causes of deaths in the Western world. Approximately one-third of these deaths are preventable by lifestyle factors, including modification of nutritional habits. Studies have demonstrated that adequate nutrition with certain types of foods containing bioactive compounds might offer significant protection against carcinogenesis. Soybeans contain a variety of phytochemicals with demonstrated anticancer activity, including isoflavones, protease inhibitors, and more recently lunasin, a novel cancer preventive seed peptide. Initially isolated from soybean, lunasin has also been reported in barley and wheat. The purpose of this review is to summarize the most recent evidence on the possible benefits of lunasin for cancer prevention.

KEYWORDS:

cancer prevention; lunasin; seeds; soy protein

PMID:

 

19787099

 

[PubMed] 
PMCID:

 

PMC2746573

 

Free PMC Article

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27.
J Agric Food Chem. 2007 Dec 26;55(26):10707-13. Epub 2007 Nov 27.

Cancer-preventive peptide lunasin from Solanum nigrum L. inhibits acetylation of core histones H3 and H4 and phosphorylation of retinoblastoma protein (Rb).

Abstract

Lunasin, a unique 43 amino acid, 4.8 kDa cancer-chemopreventive peptide initially reported in soybean and now found in barley and wheat, has been shown to be cancer-chemopreventive in mammalian cells and in a skin cancer mouse model against oncogenes and chemical carcinogens. To identify bioactive components in traditional herbal medicines and in search for new sources of lunasin, we report here the properties of lunasinfrom Solanum nigrum L. (SNL), a plant indigenous to northeast Asia. Lunasin was screened in the crude extracts of five varieties of the medicinal plants of Solanaceae origin and seven other major herbal plants. An in vitro digestion stability assay for measuring bioavailability was carried out on SNL crude protein and autoclaved SNL using pepsin and pancreatin. A nonradioactive histone acetyltransferase (HAT) assay and HAT activity colorimetric assay were used to measure the inhibition of core histone acetylation. The inhibitory effect of lunasin on the phosphorylation of retinoblastoma protein (Rb) was determined by immunoblotting against phospho-Rb. Lunasin isolated from autoclaved SNL inhibited core histone H3 and H4 acetylation, the activities of the HATs, and the phosphorylation of the Rb protein. Lunasin in the crude protein and in the autoclaved crude protein was very stable to pepsin and pancreatin in vitro digestion, while the synthetic purelunasin was digested at 2 min after the reaction. We conclude that lunasin is a bioactive and bioavailable component in SNL and that consumption of SNL may play an important role in cancer prevention.

PMID:

 

18038993

 

[PubMed – indexed for MEDLINE]
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28.
J Agric Food Chem. 2007 Dec 26;55(26):10703-6. Epub 2007 Nov 27.

In vitro digestibility of the cancer-preventive soy peptides lunasin and BBI.

Abstract

Lunasin and BBI (Bowman Birk protease inhibitor) are bioactive soy peptides that have been shown to be effective suppressors of carcinogenesis in in vitro and in vivo model systems. Since they are subject to digestion in the gastrointestinal tract, we investigated here the stabilities of lunasin and BBI to digestion in vitro by simulated intestinal fluid (SIF) and simulated gastric fluid (SGF). Samples containing lunasin and BBI of varying purities were subjected to in vitro digestion by SIF and SGF at different times and analyzed by Western blot. While the pure BBI reaction is stable after SIF and SGF digestions, the purified lunasin from soybean and synthetic lunasin are easily digested after 2 min in both in vitro digestions. In contrast, lunasinfrom soy protein containing BBI is comparatively stable after SIF and SGF digestions. Both lunasin and BBI are able to internalize into the cell and localize in the nucleus even after digestion, suggesting that some of the peptides are intact and bioactive. These data suggest that BBI plays a role in protecting lunasin from digestion when soy protein is consumed orally. The role of other soy protease inhibitors such as Kunitz Trypsin Inhibitor (KTI) cannot be excluded from these experiments.

PMID:

 

18038984

 

[PubMed – indexed for MEDLINE]
Icon for American Chemical Society
29.
Cancer Lett. 2007 Sep 18;255(1):42-8. Epub 2007 May 3.

The cancer preventive peptide lunasin from wheat inhibits core histone acetylation.

Abstract

Lunasin is a unique 43-amino acid cancer preventive peptide initially reported in soybean and barley and has been shown to be chemopreventive in mammalian cells and in a skin cancer mouse model against oncogenes and chemical carcinogens. We report here the core histone H3- and H-acetylation inhibitory properties oflunasin from wheat, a new source of the peptide and from the livers of rats fed with lunasin-enriched wheat (LEW) to measure bioavailability. A non-radioactive histone acetyl transferase assay was used to measure inhibition of core histone acetylation. The presence of lunasin in wheat was established by Western blot and identified by liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). Lunasin isolated from wheat seeds at different stages of development inhibited core histone H3 and H4 acetylation in a dose-dependent manner. Lunasin extracted from liver of rats fed with lunasin-enriched wheat (LEW) also inhibited histone acetylation confirming that the peptide is intact and bioactive. The amounts of lunasin in the developing seeds and in the rat liver correlated extremely well with the extent of inhibition of core histone acetylation.

PMID:

 

17481808

 

[PubMed – indexed for MEDLINE]
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30.
J Agric Food Chem. 2007 Feb 7;55(3):632-7.

Inhibition of core histone acetylation by the cancer preventive peptide lunasin.

Abstract

Lunasin is a unique 43 amino acid soy peptide that has been shown to be chemopreventive in mammalian cells and in a skin cancer mouse model in this work against oncogenes and chemical carcinogens. The observation that lunasin inhibits core histone acetylation led to the proposal of an epigenetic mechanism by which lunasin selectively kills cells that are being transformed by disrupting the dynamics of cellular histone acetylation-deacetylation when the transformation event is triggered by the inactivation of tumor suppressors that function via histone deacetylation. Here is reported for the first time the core histone H3- and H4-acetylation inhibitory properties of lunasin from different Korean soybean varieties used for various food purposes and from tissues of rats fed with lunasin-enriched soy (LES) to measure bioavailability. Lunasin was analyzed by immunostaining and inhibition of core histone acetylation by a non-radioactive histone acetyl transferase assay. Various amounts of lunasin are found in the soybean varieties, which correlated with the extent of inhibition of core histone acetylation. Both soy lunasin and synthetic lunasin inhibit core histone acetylation in a dose-dependent manner. Lunasin in LES is protected from in vitro digestion by pepsin. Lunasinextracted from blood and liver of rats fed with LES is intact and inhibits core histone acetylation.

PMID:

 

17263453

 

[PubMed – indexed for MEDLINE]
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31.
J Agric Food Chem. 2005 Oct 5;53(20):7686-90.

Contents and bioactivities of lunasin, bowman-birk inhibitor, and isoflavones in soybean seed.

Abstract

It has been previously demonstrated that lunasin is a novel and promising cancer preventive peptide from soybean. The Bowman-Birk protease inhibitor (BBI) and isoflavones are well-studied substances from soy. This study evaluated the levels and bioactivities of these three compounds as affected by stages of seed development and sprouting under light and dark conditions. BBI and lunasin appear at 7 and 6 weeks, respectively, after flowering and increase as the seed matures. Daidzein and genistein both decrease during seed maturation. During sprouting under light, BBI increases up to the 6th day and decreases thereafter, disappearing at the 9th day after soaking. Under dark conditions, BBI increases up to the 7th day after soaking and decreases thereafter, disappearing at the 10th day. Lunasin starts to decrease at 2 days after soaking and disappears completely at 7 days under light and dark conditions. Daidzein and genistein increase continuously during the 10 days of soaking, and both increase more in the dark than under light conditions. Protein extracts from early seed development (2-5 weeks after flowering) suppress cell viability to a greater degree than those from later stages (6-9 weeks). Inhibition of foci formation by protein extracts from later stages is greater than those from earlier stages. Lunasin and BBI suppress foci formation more than the isoflavones. Sprouting decreases lunasin and BBI contents but increases isoflavones. Protein extracts from early soaking times inhibit foci formation more and suppress cell viability less than those from later soaking times. Light and dark conditions have no influence on the bioactivities of protein extracts. These data are useful in the preparation of soy fractions enriched in lunasin, BBI, and isoflavones and in making dietary recommendations.

PMID:

 

16190617

 

[PubMed – indexed for MEDLINE]
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32.
Nutr Rev. 2005 Jan;63(1):16-21.

Lunasin: a cancer-preventive soy peptide.

Abstract

Lunasin is a novel, cancer-preventive peptide whose efficacy against chemical carcinogens and oncogenes has been demonstrated in mammalian cells and in a skin cancer mouse model. Isolated and characterized in soy, lunasin peptide is also documented in barley. Lunasin is found in all of the genotypes analyzed from the US soy germ plasm collection and in commercially available soy proteins. Pilot studies show that lunasin is bioavailable in mice and rats when orally ingested, opening the way for dietary administration in cancerprevention studies. Lunasin internalizes into mammalian cells within minutes of exogenous application, and localizes in the nucleus after 18 hours. It inhibits acetylation of core histones in mammalian cells. In spite of itscancer-preventive properties, lunasin does not affect the growth rate of normal and established cancer cell lines. An epigenetic mechanism of action is proposed whereby lunasin selectively kills cells being transformed or newly transformed by binding to deacetylated core histones exposed by the transformation event, disrupting the dynamics of histone acetylation-deacetylation and leading to cell death.

PMID:

 

15730231

 

[PubMed – indexed for MEDLINE]
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33.
Nutr Rev. 2003 Jul;61(7):239-46.

The anticarcinogenic potential of soybean lectin and lunasin.

Erratum in

  • Nutr Rev. 2003 Aug;61(8):293.

Abstract

Cancer is one of the leading causes of death worldwide, generally exceeded only by cardiovascular disease in the developed world. The number of people diagnosed with cancer within the next few decades is expected to double. There will therefore be increased demand for novel diagnostic and medical therapies that use new non-traditional sources. Soybeans contain a variety of anticarcinogenic phytochemicals. Recently, there has been increased interest in the potential health benefits of bioactive polypeptides and proteins from soybeans, including lunasin and lectins. Lunasin is a polypeptide that arrests cell division and induces apoptosis in malignant cells. Lectins are glycoproteins that selectively bind carbohydrates; lectins are used in medicine in a variety of new applications. Additional research, including clinical trials, should continue to examine and elucidate the therapeutic effects, nutritional benefits, and toxic consequences of commonly ingested soybean lectins and lunasin.

PMID:

 

12918876

 

[PubMed – indexed for MEDLINE]
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34.
Cancer Res. 2001 Oct 15;61(20):7473-8.

Chemopreventive property of a soybean peptide (lunasin) that binds to deacetylated histones and inhibits acetylation.

Abstract

Lunasin is a unique 43-amino acid soybean peptide that contains at its carboxyl end: (a) nine Asp (D) residues; (b) an Arg-Gly-Asp (RGD) cell adhesion motif; and (c) a predicted helix with structural homology to a conserved region of chromatin-binding proteins. We demonstrated previously that transfection of mammalian cells with the lunasin gene arrests mitosis, leading to cell death. Here we show that exogenous application of the lunasin peptide inhibits chemical carcinogen-induced transformation of murine fibroblast cells to cancerous foci. To elucidate its mechanism of action we show that lunasin: (a) internalizes in the cell through the RGD cell adhesion motif; (b) colocalizes with hypoacetylated chromatin; (c) binds preferentially to deacetylated histone H4 in vitro; and (d) inhibits histone H3 and H4 acetylation in vivo in the presence of a histone deacetylase inhibitor. These results suggest a mechanism whereby lunasin selectively induces apoptosis, mostly in cells undergoing transformation, by preventing histone acetylation. In support of this, lunasinselectively induces apoptosis in E1A-transfected cells but not in nontransformed cells. Finally, in the SENCAR mouse skin cancer model, dermal application of lunasin (250 microg/week) reduces skin tumor incidence by approximately 70%, decreases tumor yield/mouse, and delays the appearance of tumors by 2 weeks relative to the positive control. These results point to the role of lunasin as a new chemopreventive agent that functions possibly via a chromatin modification mechanism.

PMID:

 

11606382

 

[PubMed – indexed for MEDLINE] 

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35.
Nat Biotechnol. 1999 May;17(5):495-500.

A soybean cDNA encoding a chromatin-binding peptide inhibits mitosis of mammalian cells.

Abstract

A soybean cDNA encoding the small subunit peptide of a cotyledon-specific 2S albumin (Gm2S-1) is thought to play a role in arresting mitosis during the DNA endoreduplication and cell expansion phase of seed development. The peptide (termed lunasin) contains the cell adhesion motif Arg-Gly-Asp (RGD) followed by eight aspartic acid residues at its C-terminal end. A chimeric gene encoding the lunasin peptide tagged with green fluorescent protein (GFP) arrested cell division, caused abnormal spindle fiber elongation, chromosomal fragmentation, and cell lysis when transiently transfected into murine embryo fibroblast, murine hepatoma, and human breast cancer cells. Deletion of the polyaspartyl end abolished the antimitotic effect. Subcellular localization of lunasin and immunobinding assay using synthetic peptides revealed the preferential adherence of lunasin to chromatin. Immunofluorescence showed that kinetochore proteins were displaced from the centromere in lunasin-transfected cells. These observations suggest that lunasin binds to the chromatin, leading to disruption of kinetochore formation and inhibition of mitosis.

 

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Dr. Weeks’ Comment:   Lunasin  is an anti-cancer peptide derived from soy which has solid science behind it.   Many patients seek immune enhancing agents which also kill cancer. Sadly, most oncologists are unaware of lunasin so this summary may be helpful for those addressing cancer.  Lunasin is available from SAFALAB  by calling 360-341-2303.  “… Lunasin is…
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