The role of a soybean peptide, lunasin, in plants and its chemopreventive nature in animal

Lunasin is a unique 43-amino acid small subunit of a 2S albumin protein present in soybean. The carboxyl end of lunasin contains (a) a predicted helix with structural homology to a conserved region of chromatin binding proteins; (b) an RGD (Arg-Gly-Asp) cell adhesion motif; (c) followed by eight aspartic acid residues. Lunasin has been extensively studied in mammalian systems because of its chemopreventive property, however, little is known about its physiological role in plants. Because of lunasin's anti-mitotic activity in mammalian cells, and the temporal expression of lunasin, which coincides with the initiation of mitotic arrest and DNA endoreduplication in developing soybean cotyledons, we hypothesized that lunasin is a novel mitotic inhibitor required for DNA endoreduplication and cell expansion in storage parenchyma cells during seed development. To determine whether lunasin affects cell cycling in heterologous systems, the lunasin gene was expressed in a tobacco cell line and Arabidopsis thaliana. Transient and inducible expression of lunasin in tobacco BY-2 suspension cells, however, did not inhibit mitosis nor induced endoreduplication. Furthermore, flow cytometry of nuclei isolated from leaves and mature embryos of transgenic Arabidopsis constitutively expressing lunasin showed that lunasin does not induce endoreduplication. It is intriguing that heterologous expression of lunasin in plants does not produce any observable phenotype, whereas, transient expression of lunasin in mammalian cells lead to arrest in cell division and apoptosis; while exogenous addition of lunasin peptides prevents foci formation in mammalian cell lines exposed to mutagens and delays carcinogenesis in mice. In addition, microarray analysis shows that exogenous addition of lunasin synthetic peptides to mammalian cells up-regulates genes involved in tumor suppression and apoptosis. We conclude that lunasin's effect on cell cycle is specific to mammalian cells. There must be specific factor(s) that interact with lunasin in mammalian cells not present in plants.