Lunasin™ Suppresses E1A-Mediated Transformation of Mammalian Cells but Does Not Inhibit Growth of Immortalized and Established Cancer Cell Lines

Abstract

Lunasin, a novel and promising chemopreventive compound isolated from soybean cotyledon, is a 43-amino acid peptide that contains a -RGD-cell adhesion motif followed by 8 aspartic acid residues at the carboxyl end and a structurally conserved helix region. We showed previously that lunasin peptide applied exogenously reduces foci formation in mouse fibroblast cells treated with chemical carcinogens and inhibits skin tumorigenesis induced by chemical carcinogens in mice when applied topically. In this study, lunasin peptide applied to cell culture suppresses foci formation in E1A-transfected mouse fibroblast NIH 3T3 cells. Within 18 h of exogenous application, lunasin internalizes into the cell and localizes in the nucleus. In an initial study of genes affected by lunasin, the peptide increases p21 protein levels fivefold in cells transfected with E1A but not in untransfected cells. In contrast to its inhibitory effects on cell transformation, lunasin has no effect on growth of imicroMortalized (nontumorigenc) and established cancer cells. This is the first report that lunasin suppresses transformation of mamicroMalian cells induced by an oncogene (E1A) in addition to chemical carcinogens.

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

“…Our collective data, thus, suggest that LUN preferentially promotes apoptotic over inhibiting proliferative pathways in mammary epithelial cells, although this anti-apoptotic activity of LUN is not exclusively PTEN-mediated and may involve other yet-to-be defined mechanisms. These findings are consistent with previous reports showing that LUN stimulated apoptosis in human colon and breast cancer cells Hsieh et al 2010a) but had no effect on the growth of numerous immortalized and established cancer lines (Lam et al 2003). Our findings that sera from SPI-fed rats significantly influenced PTEN expression, PTEN nuclear localization, and cellular apoptosis, relative to sera from control diet (CAS)-fed mice are consistent with studies reporting the presence of bioactive components such as the isoflavones genistein and daidzein, and LUN in human and rodent sera after dietary soy protein intake (Jeong et al 2007;Jeong et al 2010;Dia et al 2009).…”

Soy, phytoestrogens and their impact on reproductive health

“…Other proteins or peptides present in lower amounts include enzymes such as lipoxygenase, chalcone synthase and catalase. Peptides such as lunasin (a 43 amino acid protease inhibitor) and the Bowman-Birk inhibitor (a 71 amino acid protease inhibitor) have been reported to have an anticancer capacity or an in vitro chemopreventative effect (Armstrong et al, 2003;Galvez et al, 2001;Lam et al, 2003). Some of the health benefits attributed to soy may result from the release of biologically active peptides by enzymatic proteolysis during gastrointestinal digestion or during the fermentation of soy proteins.…”

1997-2012: Fifteen Years of Research on Peptide Lunasin

“…First studies performed with mammalian cells revealed that lunasin did not affect their morphology and proliferation. However, this peptide acted preventing their transformation induced by chemical carcinogens-7,12-dimethylbenz[a]anthracene (DMBA) and 3-methylcholanthrene (MCA) [33,34], viral and ras-oncogenes [33,35,36]. These experiments made lunasin be considered a "watchdog" agent in the cell nucleus that once the transformation event occurs, it acts as a surrogate tumor suppressor that tightly binds to deacetylated core histones disrupting the balance between acetylation-deacetylation, which is perceived by the cell as abnormal and leads to cell death [37].…”