Wednesday, 21 November 2018

Lunasin

Dr. Weeks’ Comment:  The seed is the treasure chest of nature and derived from seeds in general and in this case soy bean seed in particular is a molecule called Lunasin which or more than a decade has been proven beneficial for people with cancer.  Seed have potent anticancer and anti-inflammatory properties.

Scalable Purification and Characterization of the Anticancer Lunasin Peptide from Soybean

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. …… 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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Introduction

Lunasin has been described as a 43 amino-acid peptide that is encoded within the soybean GM2S-1 gene and was first identified as a novel peptide found in soybean seed extracts [1]. Initial studies of the biological activity of lunasin found that expression constructs encoding the lunasin peptide sequence resulted in arrested cell division and the formation of nonseptated filaments in E. coli and caused mitotic arrest in mammalian cell lines, apparently by binding to kinetochore regions of the centromere and blocking microtubule attachment [2]. These initial results suggested that lunasin could be useful as a cancer therapeutic provided that lunasin could be specifically delivered to cancer cells. Given that consumption of soy products has been associated with the reduced incidence of specific cancers [3][4]; additional studies were done to examine the cancer chemoprevention activity of lunasin. In a series of key studies, addition of a synthetic lunasin peptide to mammalian cells prevented cellular transformation by chemical carcinogens and the viral oncogenes ras and E1A [5][6][7][8]. An interesting observation made during these initial studies was that neither normal immortalized cells, nor stable cancer cell lines were affected by lunasin peptide exposure. These results provided the initial indication that lunasin may be used as a chemoprevention agent. This hypothesis was further supported by animal studies in which topical application of lunasin significantly suppressed skin papilloma formation in SENCAR (SENsitivity to CARcinogenesis) mice treated with a combination of the chemical carcinogen 7,12-dimethylbenz[α]anthracene and the tumor promoter 12-O-tetradecanoylphorbol-13-acetate [5]. Since the original discovery of lunasin in soybean, lunasin has been identified in barley, wheat, Solanum nigrum, and amaranth [7][9],[10][11][12][13]. Analysis of different soybean cultivars demonstrated that lunasin content varied significantly, suggesting that it may be possible to breed soybean varieties with higher lunasin content [14][15].

More recent studies have demonstrated that lunasin can inhibit the growth of some cancer cells in culture and in a mouse xenograft model [16][17][18][19] and that it also has anti-inflammatory activity [20][21][22]. This contradicts the earlier studies which were done on a limited number of cell lines and demonstrate that the initial conclusion that lunasin did not affect established cancer cells was incorrect. These latter studies suggest that lunasin may be useful both as a chemoprevention agent and a cancer therapeutic. Lunasin has been shown to bind specifically to the deacetylated core histones H3 and H4 and current hypotheses on lunasin’s mechanism of action suggest that this is critical for the anticancer effects of lunasin [5][7][9],[23][24][25]. de Lumen and coworkers [6][24][26] have proposed a model for the molecular basis of the biological effects of lunasin based on the disruption of normal histone acetylation by histone deacetylase and histone acetylase. Recent studies have shown that treatment of cancer cells with lunasin may induce apoptosis through the intrinsic pathway [16][17][27] and that both the anti-inflammatory and anticancer effects are mediated by suppression of the NF-κB pathway [20][28]. It is not known if these effects are linked to inhibition of HAT and disruption of histone acetylation. Recent gene expression studies indicate that lunasin can affect a number of signaling pathways in different cell types, thus, some of the observed biological effects of lunasin may be independent of histone acetylation [23][29].

Although the potential anticancer effect of lunasin has been known for over a decade, little progress has been made to test in vivo efficacy of purified lunasin in animal or human clinical studies. One major limitation has been the lack of availability of the gram-kilogram quantities of highly purified lunasin required to conduct such studies. To address this need, we have developed a method for purifying lunasin from defatted soybean flour (white flake) that yields highly purified lunasin and can be easily scaled to produce kilogram quantities of peptide. The purified lunasin was biologically active as measured by histone binding assays and was found to have the same, if not higher, activity compared to synthetic lunasin. Structural analysis of the purified peptide revealed that the major form of lunasin present in soybean white flake is 44 amino acids in length and contains an additional C-terminal asparagine relative to previously published descriptions of lunasin.

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Dr. Weeks’ Comment:  The seed is the treasure chest of nature and derived from seeds in general and in this case soy bean seed in particular is a molecule called Lunasin which or more than a decade has been proven beneficial for people with cancer.  Seed have potent anticancer and anti-inflammatory properties. Scalable Purification and…
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