Lunasin

Lunasin (CAS No.: 496823-34-8) is a 43-amino acid peptide encoded by soybean 2S albumin (sequence: SKWQHQQDSCRKQLQGVNLTPCEKHIMEKIQGRGDDDDDDDDD), and is also present in plants such as wheat, barley, and amaranth. Mechanistically, it binds deacetylated histones H3/H4 through the C-terminal poly-aspartic acid region, competitively inhibits histone acetyltransferases, and exerts epigenetic regulatory effects; meanwhile, the RGD motif antagonizes integrins, inhibits the FAK/ERK/NF-κB pathway, and also has antioxidant and anti-inflammatory activities, with selective effects on transformed cells and tumor cells.

In chemical transformation experiments, nanomolar concentrations are used, which can inhibit fibroblast transformation induced by DMBA, MCA, and oncogenes, with activity superior to that of soybean BBI inhibitor. In tumor cell experiments, doses of 1~200 μM are commonly used, showing dose-dependent inhibition of cell proliferation in colon cancer (KM12L4 IC50 13 μM), breast cancer, lung cancer, and other cells, blocking the G1/S or G2/M phase, inducing apoptosis, and inhibiting tumor stem cell sphere formation; it shows no significant toxicity to normal cells.

In skin cancer models, topical application at 250 μg / week reduced tumor incidence in SENCAR mice by 70%. In xenograft models, intraperitoneal injection at 4~30 mg/kg is commonly used and can inhibit the growth of breast cancer, lung cancer, melanoma, and liver metastasis of colon cancer. Oral administration depends on the protection of peptide integrity by endogenous soybean protease inhibitors; intact peptide can enter the bloodstream and distribute to multiple tissues such as the liver and lungs, retaining biological activity.

References:

[1] Hernández-Ledesma B, Hsieh CC, de Lumen BO. Lunasin, a novel seed peptide for cancer prevention. Peptides. 2009 Feb;30(2):426-30. doi: 10.1016/j.peptides.2008.11.002. Epub 2008 Nov 13. PMID: 19056440.

[2] Fernández-Tomé S, Indiano-Romacho P, Mora-Gutiérrez I, Pérez-Rodríguez L, Ortega Moreno L, Marin AC, Baldán-Martín M, Moreno-Monteagudo JA, Santander C, Chaparro M, Hernández-Ledesma B, Gisbert JP, Bernardo D. Lunasin Peptide is a Modulator of the Immune Response in the Human Gastrointestinal Tract. Mol Nutr Food Res. 2021 Jun;65(12):e2001034. doi: 10.1002/mnfr.202001034. Epub 2021 May 13. PMID: 33890400.

[3] Alves de Souza SM, Hernández-Ledesma B, de Souza TLF. Lunasin as a Promising Plant-Derived Peptide for Cancer Therapy. Int J Mol Sci. 2022 Aug 23;23(17):9548. doi: 10.3390/ijms23179548. PMID: 36076946; PMCID: PMC9455814.

[4] Kaufman-Szymczyk A, Kaczmarek W, Fabianowska-Majewska K, Lubecka-Gajewska K. Lunasin and Its Epigenetic Impact in Cancer Chemoprevention. Int J Mol Sci. 2023 May 24;24(11):9187. doi: 10.3390/ijms24119187. PMID: 37298139; PMCID: PMC10253126.