Lunasin induces apoptosis and modifies the expression of genes associated with extracellular matrix and cell adhesion in human metastatic colon cancer cells

Scope: Lunasin is an arginine-glycine-aspartic acid (RGD) cancer preventive peptide. The objective was to evaluate the potential of lunasin to induce apoptosis in human colon cancer cells and their oxaliplatin-resistant (OxR) variants, and its effect on the expression of human extracellular matrix and adhesion genes. Methods and results: Various human colon cancer cell lines which underwent metastasis were evaluated in vitro using cell flow cytometry and fluorescence microscopy. Lunasin cytotoxicity to different colon cancer cells correlated with the expression of alpha(5)beta(1) integrin, being most potent to KM12L4 cells (IC50 = 13 mu M). Lunasin arrested cell cycle at G2/M phase with concomitant increase in the expression of cyclin-dependent kinase inhibitors p21 and p27. Lunasin (5-25 mu M) activated the apoptotic mitochondrial pathway as evidenced by changes in the expressions of Bcl-2, Bax, nuclear clusterin, cytochrome c and caspase-3 in KM12L4 and KM12L4-OxR. Lunasin increased the activity of initiator caspase-9 leading to the activation of caspase-3 and also modified the expression of human extracellular matrix and adhesion genes, downregulating integrin alpha(5), SELE, MMP10, integrin beta(2) and COL6A1 by 5.01-, 6.53-, 7.71-, 8.19- and 10.10-fold, respectively, while upregulating COL12A1 by 11.61-fold. Conclusion: Lunasin can be used in cases where resistance to chemotherapy developed.