Mode of administration affected the capability of soybean‐derived peptide lunasin to prevent metastasis of human colon cancer cells in a mouse model

Abstract

The objective was to evaluate soybean‐derived peptide lunasin to inhibit KM12L4 human colon cancer cell metastasis in mouse model of colorectal cancer. Mouse was injected with 1 × 106 KM12L4 colon cancer cells in the spleen and randomization was made after 4 days. Mice that received 4 mg lunasin/kg body weight per day (i.p.) had a reduced number of liver metastatic tumors compared to group that received PBS (P = 0.047). Liver‐tumor tissue showed lunasin (4 mg/kg bw, per day, i.p.) reduced the expression of histone H3K18 (P = 0.002) and H4K8 (P < 0.0001) with reduction in the expression of p300 enzyme (P = 0.039). Orally administered lunasin for 28 days reduced the number of liver metastatic nodules from 18 (PBS, n = 6) to 8 (8 mg/kg bw, n = 5, P = 0.293) to 1 (20 mg/kg bw, n = 3, P = 0.247); however, these values were not statistically significant. Gavage lunasin (8 mg/kg bw) did not significantly affect expression of proliferating cell nuclear antigen, pro‐apoptotic Bax, anti‐apoptotic Bcl‐2 and H3K18 and significantly increased the expression of H4K8 in liver‐tumor tissue. No liver‐tumor tissue was present for analysis after gavage lunasin (20 mg/kg bw). In conclusion, intraperitoneally‐administered lunasin (4 mg/kg bw) was effective in preventing colon cancer metastasis but not after oral administration of the bioactive peptide lunasin up to 20 mg/kg bw.Grant Funding Source: USDA