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Ben O. De Lumen - One of the best experts on this subject based on the ideXlab platform.
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Identification of chemopreventive peptide Lunasin in some Lupinus species
'Japanese Society of Applied Entomology & Zoology', 2015Co-Authors: Ramos Herrera, Óscar Javier, Ben O. De Lumen, Hernández-ledesma Blanca, Sepúlveda Jiménez Gabriela, López Laredo, Alma Rosa, Hsieh Chia-chien, Bermúdez Torres KalinaAbstract:Trabajo presentado a la 13th International Lupin Conference celebrada en Poznań (Polonia) del 6 al 10 de junio de 2011.Lupinus seeds are characterized by elevated contents of high quality protein, so they find uses in both human and animal nutrition. However, little is known about possible bioactive compounds that could be beneficial to health. Lunasin is a 43 amino acid residue peptide isolated by the group of Prof. de Lumen (University of California, Berkeley) from the albumin protein fraction of soybean. Its cancer chemopreventive properties have been demonstrated by in vitro and in vivo assays; currently other plants are being investigated as possible sources of this peptide. This study aimed to detect Lunasin in two cultivated and two wild species of Lupinus. Lunasin detection using Lunasin monoclonal antibodies was carried out on total protein extracts as well as soluble fractions of defatted flour from seeds with and without testa. Soy (Glycine max) seed extracts served as positive control. Results showed the presence of Lunasin in G. max protein fractions of albumin, globulin, and glutelin. Lunasin was found in prolamins fraction of L. albus seeds with testa; whereas it was found in albumin and glutelin fractions of seeds without testa of L. montanus and L. campestris, respectively. Lunasin was not detected in protein extracts of seeds without testa of L. albus and seed with and without testa of L. mutabilis. Peptide bands of molecular weights greater than 25 kDa were detected in the fractions of albumin, globulin and glutelin of all evaluated Lupinus species, suggesting presence of Lunasin-related peptides.This work was funded by SIP-IPN (SIP 20090435) and by CONACYT (100808). O.J. Ramos H. is indebted to Instituto Politecnico Nacional (PIFI-IPN) and CONACYT for the fellowship awarded. K. Bermudez Torres, G. Sepulveda J. and A.R. Lopez L. thank EDI and COFAAIPN for support. B. Hernandez-Ledesma thanks European Commission and Spanish National Research Council by her Marie-Curie and JAE-Doc contracts.Peer Reviewe
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Lunasin is prevalent in barley and is bioavailable and bioactive in in vivo and in vitro studies
Nutrition and Cancer, 2010Co-Authors: Hyung Jin Jeong, Jin Boo Jeong, Blanca Hernandezledesma, Chia Chien Hsieh, Ben O. De LumenAbstract:Lunasin, a unique 43-amino acid peptide found in a number of seeds, has been shown to be chemopreventive in mammalian cells and in a skin cancer mouse model. To elucidate the role of cereals in cancer prevention, we report here the prevalence, bioavailability, and bioactivity of Lunasin from barley. Lunasin is present in all cultivars of barley analyzed. The liver and kidney of rats fed with Lunasin-enriched barley (LEB) show the presence of Lunasin in Western blot. Lunasin extracted from the kidney and liver inhibits the activities of HATs (histone acetyl transferases), yGCN5 by 20% and 18% at 100 nM, and PCAF activity by 25% and 24% at 100 nM, confirming that the peptide is intact and bioactive. Purified barley Lunasin localizes in the nuclei of NIH 3T3 cells. Barley Lunasin added to NIH 3T3 cells in the presence of the chemical carcinogen MCA activates the expression of tumor suppressors p21 and p15 by 45% and 47%, decreases cyclin D1 by 98%, and inhibits Rb hyperphosphorylation by 45% compared with the MCA treatment alone. We conclude that Lunasin is prevalent in barley, bioavailable, and bioactive and that consumption of barley could play an important role of cancer prevention in barley-consuming populations.
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soybean peptide Lunasin suppresses in vitro and in vivo 7 12 dimethylbenz a anthracene induced tumorigenesis
Journal of Food Science, 2010Co-Authors: Chia Chien Hsieh, Blanca Hernandezledesma, Ben O. De LumenAbstract:: 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. Practical Application: Daily intake of Lunasin-enriched soy protein is introduced as a promising strategy to prevent chemical carcinogens-induced mammary tumors.
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amaranth Lunasin like peptide internalizes into the cell nucleus and inhibits chemical carcinogen induced transformation of nih 3t3 cells
Peptides, 2010Co-Authors: Enrique Maldonadocervantes, Hyung Jin Jeong, Ben O. De Lumen, Elvira Gonzalez De Mejia, Fabiola Leongalvan, Alberto Barrerapacheco, Antonio De Leonrodriguez, Ana Barba P De La RosaAbstract:Because an unbalanced diet is an important risk factor for several illnesses, interest has increased in finding novel health-promoting foods. Amaranth produces seeds that not only have substantial nutritional properties but that also contain phytochemical compounds as rutin and nicotiflorin and peptides with antihypertensive and anticarcinogenic activities. We report that a cancer-preventive peptide in amaranth has activities similar to those of soybean Lunasin. The amaranth Lunasin-like peptide, however, requires less time than the soybean Lunasin to internalize into the nucleus of NIH-3T3 cells, and inhibits histone acetylation (H(3) and H(4) in a 70 and 77%, respectively). The amaranth Lunasin-like peptide inhibited the transformation of NIH-3T3 cells to cancerous foci. The open reading frame (ORF) of amaranth Lunasin corresponds to a bifunctional inhibitor/lipid-transfer protein (LTP). LTPs are a family of proteins that in plants are implicated in different functions, albeit all linked to developmental processes and biotic and abiotic stress resistance. Our results open new intriguing questions about the function of Lunasin in plants and support that amaranth is a food alternative containing natural peptides with health-promoting benefits.
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Lunasin peptide purified from solanum nigrum l protects dna from oxidative damage by suppressing the generation of hydroxyl radical via blocking fenton reaction
Cancer Letters, 2010Co-Authors: Jin Boo Jeong, Ben O. De Lumen, Hyung Jin JeongAbstract:Abstract Oxidative DNA damage is the most critical factor implicated in carcinogenesis and other disorders. However, the protective effects of Lunasin against oxidative DNA damage have not yet reported. In this study, we report here the protective effect of Lunasin purified from Solanum nigrum L. against oxidative DNA. Lunasin protected DNA from the oxidative damage induced by Fe 2+ ion and hydroxyl radical. To better understand the mechanism for the protective effect of Lunasin against DNA damage, the abilities to chelate Fe 2+ , scavenge the generated hydroxyl radical and block the generation of hydroxyl radical were evaluated. Although it did not scavenge generated hydroxyl radical, Lunasin blocked the generation of hydroxyl radical by chelating Fe 2+ ion. We conclude that Lunasin protects DNA from oxidation by blocking fenton reaction between Fe 2+ and H 2 O 2 by chelating Fe 2+ and that consumption of Lunasin may play an important role in the chemoprevention for the oxidative carcinogenesis.
Elvira Gonzalez De Mejia - One of the best experts on this subject based on the ideXlab platform.
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potential health benefits associated with Lunasin concentration in dietary supplements and Lunasin enriched soy extract
Nutrients, 2021Co-Authors: Elvira Gonzalez De Mejia, Vermont P Dia, Erick Damian Castanedareyes, Luis Mojica, Hui Wang, Toni Wang, Lawrence A JohnsonAbstract:Lunasin has demonstrated antioxidative, anti-inflammatory, and chemopreventive properties. The objectives were to evaluate the concentration of Lunasin in different Lunasin-based commercial dietary supplements, to produce a Lunasin-enriched soy extract (LESE) using a two-step pilot-plant-based ultrafiltration process, and to evaluate their biological potential in vitro. LESE was produced using 30 and 1 kDa membranes in a custom-made ultrafiltration skid. Lunasin was quantified in eight products and LESE. Lunasin concentrations of the Lunasin-based products ranged from 9.2 ± 0.6 to 25.7 ± 1.1 mg Lunasin/g protein. The LESE extract contained 58.2 mg Lunasin/g protein, up to 6.3-fold higher Lunasin enrichment than Lunasin-based dietary supplements. Antioxidant capacity ranged from 121.5 mmol Trolox equivalents (TE)/g in Now® Kids to 354.4 mmol TE/g in LESE. Histone acetyltransferase (HAT) inhibition ranged from 5.3% on Soy Sentials® to 38.3% on synthetic Lunasin. ORAC and Lunasin concentrations were positively correlated, and HAT and Lunasin concentrations were negatively correlated (p < 0.05). Melanoma B16-F10 and A375 cells treated with Lunasin showed dose-dependent inhibitory potential (IC50 equivalent to 330 and 370 μM Lunasin, respectively). Lunasin showed protein kinase B expression (57 ± 14%) compared to the control (100%) in B16-F10. Lunasin concentration found in commercial products and Lunasin-enriched soy extract could exert benefits to consumers.
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Endocytic mechanism of internalization of dietary peptide Lunasin into macrophages in inflammatory condition associated with cardiovascular disease. PLoS One 2013
2016Co-Authors: Anthony Cam, I Sivaguru, Elvira Gonzalez De MejiaAbstract:Cardiovascular disease (CVD) is the leading cause of death in the United States. Diet influences risk factors associated with CVD and atherosclerosis, a major vascular disease that arises from inflammation. Lunasin, a peptide derived from plant foods such as soybeans, contains a unique Arg-Gly-Asp cell-adhesion motif and inhibits the pathways involved in the inflammatory cascade. The objective was to determine the mechanism by which Lunasin is internalized into human THP-1 macrophages, investigate the expression of endocytic membrane proteins in inflammatory conditions and to identify the pathways involved. While lipopolysaccharide (10 nM), vitronectin (130 nM) and a combination of these two molecules enhanced Lunasin uptake and increased basal aVb3 integrin expression, Lunasin reduced aVb3 expression by 25.5, 26.8 and 49.2%, respectively. The pretreatment of cells with brefeldin A (71 mM), an inhibitor of protein trafficking, inhibited Lunasin internalization by up to 99.8%. Lunasin increased caveolin-1 expression by up to 204.8%, but did not modulate clathrin. The pretreatment of macrophages with nystatin (54 mM), an inhibitor of caveolae-dependent endocytosis, reduced Lunasin internalization. The presence of amantadine (1 mM) and amiloride (1 mM), inhibitors of clathrin-mediated endocytosis and macropinocytosis, abolished Lunasin cell entry. Lunasin elicited a transient reduction in intracellular levels of Ca2+ in LPS-induced macrophages. The results suggest that internalization of Lunasin into macrophages is amplified in inflammatory conditions and is primarily mediated by endocytic mechanisms that involve integrin signaling, clathrin-coated structure
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endocytic mechanism of internalization of dietary peptide Lunasin into macrophages in inflammatory condition associated with cardiovascular disease
PLOS ONE, 2013Co-Authors: Mayandi Sivaguru, Elvira Gonzalez De MejiaAbstract:Cardiovascular disease (CVD) is the leading cause of death in the United States. Diet influences risk factors associated with CVD and atherosclerosis, a major vascular disease that arises from inflammation. Lunasin, a peptide derived from plant foods such as soybeans, contains a unique Arg-Gly-Asp cell-adhesion motif and inhibits the pathways involved in the inflammatory cascade. The objective was to determine the mechanism by which Lunasin is internalized into human THP-1 macrophages, investigate the expression of endocytic membrane proteins in inflammatory conditions and to identify the pathways involved. While lipopolysaccharide (10 nM), vitronectin (130 nM) and a combination of these two molecules enhanced Lunasin uptake and increased basal αVβ3 integrin expression, Lunasin reduced αVβ3 expression by 25.5, 26.8 and 49.2%, respectively. The pretreatment of cells with brefeldin A (71 µM), an inhibitor of protein trafficking, inhibited Lunasin internalization by up to 99.8%. Lunasin increased caveolin-1 expression by up to 204.8%, but did not modulate clathrin. The pretreatment of macrophages with nystatin (54 µM), an inhibitor of caveolae-dependent endocytosis, reduced Lunasin internalization. The presence of amantadine (1 mM) and amiloride (1 mM), inhibitors of clathrin-mediated endocytosis and macropinocytosis, abolished Lunasin cell entry. Lunasin elicited a transient reduction in intracellular levels of Ca2+ in LPS-induced macrophages. The results suggest that internalization of Lunasin into macrophages is amplified in inflammatory conditions and is primarily mediated by endocytic mechanisms that involve integrin signaling, clathrin-coated structures and macropinosomes. Lunasin may be responsible for attenuation of CVD risk factors by interacting with pathways involved in endocytosis and inflammation.
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potential of Lunasin orally administered in comparison to intraperitoneal injection to inhibit colon cancer metastasis in vivo
Journal of Cancer Therapy, 2013Co-Authors: Vermont P Dia, Elvira Gonzalez De MejiaAbstract:Lunasin is a bioactive peptide originally isolated from soybean and has demonstrated chemopreventive and anti-cancer properties against skin, colon and breast cancers. The objective of the study was to evaluate the capability of intraperitoneally and orally-administered soybean-derived peptide Lunasin to inhibit KM12L4 human colon cancer cell metastasis in a mouse model. Intraperitoneal (i.p.) injection of Lunasin (4 mg/kg bw/day) reduced the number of liver metastasis by 50% (P = 0.047) and the liver weight/body weight ratio by 23% (P = 0.039). Oral administration of Lunasin reduced the number of liver metastasis by 56% (8 mg/kg bw/day, P = 0.293) and 94% (20 mg/kg bw/day, P = 0.247). Immunohistochemical staining of the liver-tissue section showed that Lunasin at 20 mg/kg bw dose did not significantly reduce the expression of proliferating cell nuclear antigen, increased the expression of proapoptotic Bax by 2.7-fold but also increased the expression of the antiapoptotic Bcl-2 by 3.8-fold. Regarding epigenetic markers, H3K18 was not significantly affected by either oral dose while H4K8 was dose dependently increased by 2.3-fold (P = 0.001, 8 mg/kg bw) and 2.7-fold (P s of administration used leading to digestion of Lunasin when given by oral gavage. In conclusion, Lunasin reduced colon cancer metastasis in vivo; however, more studies are needed to determine the oral dose of Lunasin and prevent colon cancer metastasis.
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structural property of soybean Lunasin and development of a method to quantify Lunasin in plasma using an optimized immunoassay protocol
Food Chemistry, 2013Co-Authors: Vermont P Dia, Sarah Franklandsearby, Francisco Laso Del Hierro, Guadalupe Garcia, Elvira Gonzalez De MejiaAbstract:Abstract Lunasin is a 43-amino acid naturally occurring chemopreventive peptide with demonstrated anti-cancer and anti-inflammatory properties. The objectives of this study were to determine the effect of temperature on the secondary structure of Lunasin, to develop a method of isolating Lunasin from human plasma using an ion-exchange microspin column and to quantify the amount of Lunasin using an optimized enzyme-linked immunosorbent assay. Lunasin was purified using a combination of ion-exchange chromatography, ultrafiltration and gel filtration chromatography. Circular dichroism showed that increased in temperature from 25 to 100 °C resulted in changes on the secondary structure of Lunasin and its capability to interact with rabbit polyclonal antibody. Enzyme linked immunosorbent assay showed that Lunasin rabbit polyclonal antibody has a titer of 250 and a specific activity of 0.05 mL/μg. A linear response was detected between 16 to 48 ng Lunasin per mL ( y = 0.03 x − 0.38, R 2 = 0.96). The use of diethylaminoethyl microspin column to isolate spiked Lunasin in human plasma showed that most Lunasin (37.8–46.5%) bound to the column eluted with Tris–HCl buffer, pH 7.5 with a yield up to 76.6%. In conclusion, Lunasin can be isolated from human plasma by a simple DEAE microspin column technique and can be quantified using a validated and optimized immunoassay procedure. This method can be used directly to quantify Lunasin from plasma in different human and animal studies aiming to determine its bioavailability.
Hyung Jin Jeong - One of the best experts on this subject based on the ideXlab platform.
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Lunasin is prevalent in barley and is bioavailable and bioactive in in vivo and in vitro studies
Nutrition and Cancer, 2010Co-Authors: Hyung Jin Jeong, Jin Boo Jeong, Blanca Hernandezledesma, Chia Chien Hsieh, Ben O. De LumenAbstract:Lunasin, a unique 43-amino acid peptide found in a number of seeds, has been shown to be chemopreventive in mammalian cells and in a skin cancer mouse model. To elucidate the role of cereals in cancer prevention, we report here the prevalence, bioavailability, and bioactivity of Lunasin from barley. Lunasin is present in all cultivars of barley analyzed. The liver and kidney of rats fed with Lunasin-enriched barley (LEB) show the presence of Lunasin in Western blot. Lunasin extracted from the kidney and liver inhibits the activities of HATs (histone acetyl transferases), yGCN5 by 20% and 18% at 100 nM, and PCAF activity by 25% and 24% at 100 nM, confirming that the peptide is intact and bioactive. Purified barley Lunasin localizes in the nuclei of NIH 3T3 cells. Barley Lunasin added to NIH 3T3 cells in the presence of the chemical carcinogen MCA activates the expression of tumor suppressors p21 and p15 by 45% and 47%, decreases cyclin D1 by 98%, and inhibits Rb hyperphosphorylation by 45% compared with the MCA treatment alone. We conclude that Lunasin is prevalent in barley, bioavailable, and bioactive and that consumption of barley could play an important role of cancer prevention in barley-consuming populations.
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amaranth Lunasin like peptide internalizes into the cell nucleus and inhibits chemical carcinogen induced transformation of nih 3t3 cells
Peptides, 2010Co-Authors: Enrique Maldonadocervantes, Hyung Jin Jeong, Ben O. De Lumen, Elvira Gonzalez De Mejia, Fabiola Leongalvan, Alberto Barrerapacheco, Antonio De Leonrodriguez, Ana Barba P De La RosaAbstract:Because an unbalanced diet is an important risk factor for several illnesses, interest has increased in finding novel health-promoting foods. Amaranth produces seeds that not only have substantial nutritional properties but that also contain phytochemical compounds as rutin and nicotiflorin and peptides with antihypertensive and anticarcinogenic activities. We report that a cancer-preventive peptide in amaranth has activities similar to those of soybean Lunasin. The amaranth Lunasin-like peptide, however, requires less time than the soybean Lunasin to internalize into the nucleus of NIH-3T3 cells, and inhibits histone acetylation (H(3) and H(4) in a 70 and 77%, respectively). The amaranth Lunasin-like peptide inhibited the transformation of NIH-3T3 cells to cancerous foci. The open reading frame (ORF) of amaranth Lunasin corresponds to a bifunctional inhibitor/lipid-transfer protein (LTP). LTPs are a family of proteins that in plants are implicated in different functions, albeit all linked to developmental processes and biotic and abiotic stress resistance. Our results open new intriguing questions about the function of Lunasin in plants and support that amaranth is a food alternative containing natural peptides with health-promoting benefits.
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Lunasin peptide purified from solanum nigrum l protects dna from oxidative damage by suppressing the generation of hydroxyl radical via blocking fenton reaction
Cancer Letters, 2010Co-Authors: Jin Boo Jeong, Ben O. De Lumen, Hyung Jin JeongAbstract:Abstract Oxidative DNA damage is the most critical factor implicated in carcinogenesis and other disorders. However, the protective effects of Lunasin against oxidative DNA damage have not yet reported. In this study, we report here the protective effect of Lunasin purified from Solanum nigrum L. against oxidative DNA. Lunasin protected DNA from the oxidative damage induced by Fe 2+ ion and hydroxyl radical. To better understand the mechanism for the protective effect of Lunasin against DNA damage, the abilities to chelate Fe 2+ , scavenge the generated hydroxyl radical and block the generation of hydroxyl radical were evaluated. Although it did not scavenge generated hydroxyl radical, Lunasin blocked the generation of hydroxyl radical by chelating Fe 2+ ion. We conclude that Lunasin protects DNA from oxidation by blocking fenton reaction between Fe 2+ and H 2 O 2 by chelating Fe 2+ and that consumption of Lunasin may play an important role in the chemoprevention for the oxidative carcinogenesis.
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the cancer preventive seed peptide Lunasin from rye is bioavailable and bioactive
Nutrition and Cancer, 2009Co-Authors: Hyung Jin Jeong, Jin Boo Jeong, Jae Ho Park, Youngkeun Cheong, Ben O. De LumenAbstract: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 of Lunasin and to better understand the role of cereals in cancer prevention, we report here the properties of Lunasin 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 of cancer prevention in rye-consuming populations.
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effect of Lunasin extracted from millet panicum miliaceum on the activity of histone acetyltransferases ygcn5 and p caf
Korean Journal of Plant Resources, 2009Co-Authors: Jae Ho Park, Ben O. De Lumen, Jin Boo Jeong, Jeong Rak Lee, Hyung Jin JeongAbstract:Lunasin is a unique 43-amino acid peptide which has shown a chemopreventive in mammalian cells and in a skin cancer mouse model. In search for new sources of Lunasin and the role of cereals in cancer prevention, we report here the properties of Lunasin purified from millet. Stability of millet Lunasin was measured by in vitro digestibility assay using pepsin and pancreatin. Inhibition of HAT (histone acetyltransferase) and nuclear localization in mammalian cells were used to measure Lunasin bioactivity as the cancer chemopreventive agent. Lunasin present in millet crude protein was stable to pepsin and pancreatin in in vitro digestion and inhibited the activities of HATs. When added exogenously, Lunasin purified from millet internalized in the nuclei of mouse fibroblast cells. On the base of this result, we conclude that Lunasin in millet is bioactive and consumption of millet may play an important role on cancer prevention in millet-consuming populations.
Vermont P Dia - One of the best experts on this subject based on the ideXlab platform.
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potential health benefits associated with Lunasin concentration in dietary supplements and Lunasin enriched soy extract
Nutrients, 2021Co-Authors: Elvira Gonzalez De Mejia, Vermont P Dia, Erick Damian Castanedareyes, Luis Mojica, Hui Wang, Toni Wang, Lawrence A JohnsonAbstract:Lunasin has demonstrated antioxidative, anti-inflammatory, and chemopreventive properties. The objectives were to evaluate the concentration of Lunasin in different Lunasin-based commercial dietary supplements, to produce a Lunasin-enriched soy extract (LESE) using a two-step pilot-plant-based ultrafiltration process, and to evaluate their biological potential in vitro. LESE was produced using 30 and 1 kDa membranes in a custom-made ultrafiltration skid. Lunasin was quantified in eight products and LESE. Lunasin concentrations of the Lunasin-based products ranged from 9.2 ± 0.6 to 25.7 ± 1.1 mg Lunasin/g protein. The LESE extract contained 58.2 mg Lunasin/g protein, up to 6.3-fold higher Lunasin enrichment than Lunasin-based dietary supplements. Antioxidant capacity ranged from 121.5 mmol Trolox equivalents (TE)/g in Now® Kids to 354.4 mmol TE/g in LESE. Histone acetyltransferase (HAT) inhibition ranged from 5.3% on Soy Sentials® to 38.3% on synthetic Lunasin. ORAC and Lunasin concentrations were positively correlated, and HAT and Lunasin concentrations were negatively correlated (p < 0.05). Melanoma B16-F10 and A375 cells treated with Lunasin showed dose-dependent inhibitory potential (IC50 equivalent to 330 and 370 μM Lunasin, respectively). Lunasin showed protein kinase B expression (57 ± 14%) compared to the control (100%) in B16-F10. Lunasin concentration found in commercial products and Lunasin-enriched soy extract could exert benefits to consumers.
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kunitz trypsin inhibitor in addition to bowman birk inhibitor influence stability of Lunasin against pepsin pancreatin hydrolysis
Food Research International, 2016Co-Authors: Samuel James Price, Hari B. Krishnan, Philipus Pangloli, Vermont P DiaAbstract:Soybean contains several biologically active components and one of this belongs to the bioactive peptide group. The objectives of this study were to produce different Lunasin-enriched preparations (LEP) and determine the effect of Bowman-Birk inhibitor (BBI) and Kunitz trypsin inhibitor (KTI) concentrations on the stability of Lunasin against pepsin-pancreatin hydrolysis (PPH). In addition, the effect of KTI mutation on Lunasin stability against PPH was determined. LEP were produced by calcium and pH precipitation methods of 30% aqueous ethanol extract from defatted soybean flour. LEP, Lunasin-enriched commercially available products and KTI control and mutant flours underwent PPH and samples were taken after pepsin and pepsin-pancreatin hydrolysis. The concentrations of BBI, KTI, and Lunasin all decreased after hydrolysis, but they had varying results. BBI concentration ranged from 167.5 to 655.8μg/g pre-hydrolysis and 171.5 to 250.1μg/g after hydrolysis. KTI concentrations ranged from 0.3 to 122.3μg/g pre-hydrolysis and 9.0 to 18.7μg/g after hydrolysis. Lunasin concentrations ranged from 8.5 to 71.0μg/g pre-hydrolysis and 4.0 to 13.2μg/g after hydrolysis. In all products tested, Lunasin concentration after PPH significantly correlated with BBI and KTI concentrations. Mutation in two KTI isoforms led to a lower concentration of Lunasin after PPH. This is the first report on the potential role of KTI in Lunasin stability against PPH and must be considered in designing Lunasin-enriched products that could potentially survive digestion after oral ingestion.
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potential of Lunasin orally administered in comparison to intraperitoneal injection to inhibit colon cancer metastasis in vivo
Journal of Cancer Therapy, 2013Co-Authors: Vermont P Dia, Elvira Gonzalez De MejiaAbstract:Lunasin is a bioactive peptide originally isolated from soybean and has demonstrated chemopreventive and anti-cancer properties against skin, colon and breast cancers. The objective of the study was to evaluate the capability of intraperitoneally and orally-administered soybean-derived peptide Lunasin to inhibit KM12L4 human colon cancer cell metastasis in a mouse model. Intraperitoneal (i.p.) injection of Lunasin (4 mg/kg bw/day) reduced the number of liver metastasis by 50% (P = 0.047) and the liver weight/body weight ratio by 23% (P = 0.039). Oral administration of Lunasin reduced the number of liver metastasis by 56% (8 mg/kg bw/day, P = 0.293) and 94% (20 mg/kg bw/day, P = 0.247). Immunohistochemical staining of the liver-tissue section showed that Lunasin at 20 mg/kg bw dose did not significantly reduce the expression of proliferating cell nuclear antigen, increased the expression of proapoptotic Bax by 2.7-fold but also increased the expression of the antiapoptotic Bcl-2 by 3.8-fold. Regarding epigenetic markers, H3K18 was not significantly affected by either oral dose while H4K8 was dose dependently increased by 2.3-fold (P = 0.001, 8 mg/kg bw) and 2.7-fold (P s of administration used leading to digestion of Lunasin when given by oral gavage. In conclusion, Lunasin reduced colon cancer metastasis in vivo; however, more studies are needed to determine the oral dose of Lunasin and prevent colon cancer metastasis.
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structural property of soybean Lunasin and development of a method to quantify Lunasin in plasma using an optimized immunoassay protocol
Food Chemistry, 2013Co-Authors: Vermont P Dia, Sarah Franklandsearby, Francisco Laso Del Hierro, Guadalupe Garcia, Elvira Gonzalez De MejiaAbstract:Abstract Lunasin is a 43-amino acid naturally occurring chemopreventive peptide with demonstrated anti-cancer and anti-inflammatory properties. The objectives of this study were to determine the effect of temperature on the secondary structure of Lunasin, to develop a method of isolating Lunasin from human plasma using an ion-exchange microspin column and to quantify the amount of Lunasin using an optimized enzyme-linked immunosorbent assay. Lunasin was purified using a combination of ion-exchange chromatography, ultrafiltration and gel filtration chromatography. Circular dichroism showed that increased in temperature from 25 to 100 °C resulted in changes on the secondary structure of Lunasin and its capability to interact with rabbit polyclonal antibody. Enzyme linked immunosorbent assay showed that Lunasin rabbit polyclonal antibody has a titer of 250 and a specific activity of 0.05 mL/μg. A linear response was detected between 16 to 48 ng Lunasin per mL ( y = 0.03 x − 0.38, R 2 = 0.96). The use of diethylaminoethyl microspin column to isolate spiked Lunasin in human plasma showed that most Lunasin (37.8–46.5%) bound to the column eluted with Tris–HCl buffer, pH 7.5 with a yield up to 76.6%. In conclusion, Lunasin can be isolated from human plasma by a simple DEAE microspin column technique and can be quantified using a validated and optimized immunoassay procedure. This method can be used directly to quantify Lunasin from plasma in different human and animal studies aiming to determine its bioavailability.
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analysis of Lunasin in commercial and pilot plant produced soybean products and an improved method of Lunasin purification
Journal of Food Science, 2012Co-Authors: Ariel Cavazos, Vermont P Dia, Elsy Morales, Elvira Gonzalez De MejiaAbstract:Lunasin is a bioactive peptide present in soybean. It is important to quantify Lunasin concentration in soy products to assess its potential impact as functional food. The objectives of this study were to analyze Lunasin in commercial soymilk products and implement an efficient method to isolate and purify it from defatted soybean flour. Defatted soybean flour was suspended in water, and the extract was loaded in a pre-equilibrated diethylaminoethyl column and bound proteins eluted using a step gradient of salt. Most Lunasin was eluted from the column at 0.2 to 0.4M NaCl as quantified by immunoassays and purified using ultracentrifugation and ultrafiltration techniques. Lunasin purity was ≥90% and a standard curve was used to quantify its concentration in soymilk products. Concentration of Lunasin in soy products, including organic soymilk, soy protein shakes, and soy infant formulas, ranged from 1.78 to 9.26 mg Lunasin/100 g product. The concentration per serving ranged from 1.59 ± 0.01 to 22.23 ± 0.74 mg Lunasin with variability depending on brand and size per serving. Steam-ground-cooked soy had the highest concentration of Lunasin (22.23 ± 0.74 mg/serving), similar to some commercial products. Ground-cooked soymilk contained roughly half the concentration of Lunasin (14.39 ± 1.4 mg/serving). Soy infant formulas that used soy protein isolate revealed lower concentrations of Lunasin (P < 0.05). It was concluded that all soymilk products analyzed contained Lunasin, and a more efficient method to isolate Lunasin with higher purity was developed.
Keith R Davis - One of the best experts on this subject based on the ideXlab platform.
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development of the plant derived peptide Lunasin as an anticancer agent
Current Opinion in Pharmacology, 2018Co-Authors: Saleha B Vuyyuri, Chris Shidal, Keith R DavisAbstract:The health benefits of soy consumption have long been recognized. An important potential benefit is the linkage of soy consumption with reduced cancer risk. One emerging factor that may confer the anticancer effects of soy is the peptide Lunasin. Lunasin has both chemopreventive and therapeutic activities against a variety of carcinogens and cancer types. A novel feature of Lunasin is that it contains multiple functional domains that can modulate gene expression through effects on histone acetylation and integrin signaling. Recent studies suggest that Lunasin effects on integrin signaling in cancer stem cells reduce expression of stemness factors with a concomitant reduction in metastatic potential. Here, we highlight recent studies of the potential use of Lunasin as an anticancer agent and its mode of action.
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the soy derived peptide Lunasin inhibits invasive potential of melanoma initiating cells
Oncotarget, 2017Co-Authors: Chris Shidal, Junichi Inaba, Kavitha Yaddanapudi, Keith R DavisAbstract:Lunasin is a 44 amino acid peptide with multiple functional domains including an aspartic acid tail, an RGD domain, and a chromatin-binding helical domain. We recently showed that Lunasin induced a phenotype switch of cancer initiating cells (CIC) out of the stem compartment by inducing melanocyte-associated differentiation markers while simultaneously reducing stem-cell-associated transcription factors. In the present study, we advance the hypothesis that Lunasin can reduce pools of melanoma cells with stem cell-like properties, and demonstrate that Lunasin treatment effectively inhibits the invasive potential of CICs in vitro as well as in vivo in a mouse experimental metastasis model. Mice receiving Lunasin treatment had significantly reduced pulmonary colonization after injection of highly metastatic B16-F10 melanoma cells compared to mice in the control group. Mechanistic studies demonstrate that Lunasin reduced activating phosphorylations of the intracellular kinases FAK and AKT as well as reduced histone acetylation of lysine residues in H3 and H4 histones. Using peptides with mutated activity domains, we functionally demonstrated that the RGD domain is necessary for Lunasin uptake and its ability to inhibit oncosphere formation by CICs, thus confirming that Lunasin's ability to affect CICs is at least in part due to the suppression of integrin signaling. Our studies suggest that Lunasin represents a unique anticancer agent that could be developed to help prevent metastasis and patient relapse by reducing the activity of CICs which are known to be resistant to current chemotherapies.
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validation of syngeneic mouse models of melanoma and non small cell lung cancer for investigating the anticancer effects of the soy derived peptide Lunasin
F1000Research, 2016Co-Authors: Bharat Devapatla, Kavitha Yaddanapudi, Chris Shidal, Keith R DavisAbstract:Background : Lunasin is a naturally occurring peptide present in soybean that has both chemopreventive and therapeutic activities that can prevent cellular transformation and inhibit the growth of several human cancer types. Recent studies indicate that Lunasin has several distinct potential modes of action including suppressing integrin signaling and epigenetic effects driven by modulation of histone acetylation. In addition to direct effects on cancer cells, Lunasin also has effects on innate immunity that may contribute to its ability to inhibit tumor growth in vivo. Methods: Standard assays for cell proliferation and colony formation were used to assess Lunasin's in vitro activity against murine Lewis lung carcinoma (LLC) and B16-F0 melanoma cells. Lunasin's in vivo activity was assessed by comparing the growth of tumors initiated by subcutaneous implantation of LLC or B16-F0 cells in Lunasin-treated and untreated C57BL/6 mice. Results: Lunasin was found to inhibit growth of murine LLC cells and murine B16-F0 melanoma cells in vitro and in wild-type C57BL/6 mice. The effects of Lunasin in these two mouse models were very similar to those previously observed in studies of human non-small cell lung cancer and melanoma cell lines. Conclusions: We have now validated two established syngeneic mouse models as being responsive to Lunasin treatment. The validation of these two in vivo syngeneic models will allow detailed studies on the combined therapeutic and immune effects of Lunasin in a fully immunocompetent mouse model.
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Scalable purification and characterization of the anticancer Lunasin peptide from soybean. PLoS One 2012
2016Co-Authors: Lauren E Seber, Elizabeth J Mcconnell, Steven D Hume, Jian Cai, Kati Boles, Brian W. Barnett, Keith R DavisAbstract: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 of Lunasin 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
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Lunasin a multifunctional anticancer peptide from soybean
International Journal of Cancer Therapy and Oncology, 2016Co-Authors: Keith R Davis, Junichi InabaAbstract:Lunasin is a bioactive peptide that was originally isolated from soybean and has since been shown to have a number of biological activities, including both cancer chemopreventive and therapeutic activities. Our recent focus has been on determining the range of cancer types that Lunasin can affect and the mechanism of action against specific cancers. We recently found that Lunasin has significant therapeutic activity against non-small cell lung cancer (NSCLC) both in vitro and in vivo. Mechanistic studies using Lunasin-sensitive and Lunasin-resistant NSCLC cell lines revealed the Lunasin blocks cell proliferation by inhibiting cell cycle progression at the G1/S phase interface and that this inhibition was associated with reduced Akt signaling. In addition, we found that these effects were linked to the inhibition of integrin signaling through αv-containing integrins. Our results provide strong support for the hypothesis that direct effects on integrin signaling represent a major mode of action responsible for Lunasin’s anticancer activity.
