Lunasin as a Promising Plant-Derived Peptide for Cancer Therapy.

Cancer has become one of the main public health problems worldwide, demanding the development of new therapeutic agents that can help reduce mortality. Lunasin is a soybean peptide that has emerged as an attractive option because its preventive and therapeutic actions against cancer. In this review, we evaluated available research on lunasin's structure and mechanism of action, which should be useful for the development of lunasin-based therapeutic products. We described data on its primary, secondary, tertiary, and possible quaternary structure, susceptibility to post-translational modifications, and structural stability. These characteristics are important for understanding drug activity and characterizing lunasin products. We also provided an overview of research on lunasin pharmacokinetics and safety. Studies examining lunasin's mechanisms of action against cancer were reviewed, highlighting reported activities, and known molecular partners. Finally, we briefly discussed commercially available lunasin products and potential combination therapeutics.

Proteomic Characterization of a Lunasin-Enriched Soybean Extract Potentially Useful in the Treatment of Helicobacter pylori Infection.

Helicobacter pylori infection affects over 50% of the world's population and leads to chronic inflammation and gastric disorders, being the main pathogen correlated to gastric cancer development. Increasing antibiotic resistance levels are a major global concern and alternative treatments are needed. Soybean peptides and other compounds might be an alternative in the treatment to avoid, eradicate and/or control symptoms of H. pylori infection. This study aimed to characterize a lunasin-enriched soybean extract (LSE) using proteomics tools and to evaluate its antioxidant, anti-inflammatory and antibacterial properties against H. pylori infection. By LC-MS/MS analysis, 124 proteins were identified, with 2S albumin (lunasin and large-chain subunits) being the fourth most abundant protein (8.9%). Lunasin consists of 44 amino acid residues and an intramolecular disulfide bond. LSE at a low dose (0.0625 mg/mL) reduced ROS production in both H. pylori-infected and non-infected AGS gastric cells. This led to a significant reduction of 6.71% in the levels of pro-inflammatory interleukin (IL)-8. LSE also showed antibacterial activity against H. pylori, which can be attributed to other soybean proteins and phenolic compounds. Our findings suggest that LSE might be a promising alternative in the management of H. pylori infection and its associated symptoms.

Physicochemical and structural properties of lunasin revealed by spectroscopic, chromatographic and molecular dynamics approaches.

Lunasin is a 43-amino acid peptide from seeds and grains with bioavailability in humans and potent chemotherapeutic action against several cancer cell lines. Here, we investigate new information about the physicochemical and structural properties of lunasin using circular dichroism (CD), fluorescence spectroscopy, electrospray ionization-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS), size exclusion chromatography (SEC), molecular dynamics (MD), and bioinformatics. CD analysis and disorder prediction obtained by PONDR indicate that lunasin has a mostly unordered structure. Double wavelength [θ]222nm x [θ]200nm plot data suggests that lunasin is an intrinsically disordered peptide (IDP) in a pre-molten globule-like (PMG-like) state, while CD spectrum deconvolution and MD simulation indicate small ß-strand content. The presence of residual structure was supported by loss of CD signal at 222 nm after treatment with urea and by increasing fluorescence emission upon bis-ANS binding. Lunasin also demonstrated stability to heating up to the temperature of 100 °C, as verified by CD. MD and CD analyses in the presence of TFE and MoRFpred prediction indicated the helix propensity of lunasin. ESI-IMS-MS data revealed that lunasin shows a propensity to form disulfide bonds at the conditions used. MD data also indicated that disulfide bond formation affects the adopted structure, showing a possible role of aspartyl-end in structure stabilization and compaction. In conclusion, our data support a characterization of lunasin as a peptide with an intrinsic disorder in a PMG-like state and reveal new aspects about its structural stability and plasticity, as well as the effects of disulfide bond formation and electrostatic attractions.