Potential of Lunasin Orally-Administered in Comparison to Intraperitoneal Injection to Inhibit Colon Cancer Metastasis in Vivo

Abstract

Lunasin is a bioactive peptide originally isolated from soybean and has demonstrated chemopreventive and anti-cancer properties against skin, colon and breast cancers. The objective of the study was to evaluate the capability of intraperi- toneally and orally-administered soybean-derived peptide lunasin to inhibit KM12L4 human colon cancer cell metasta- sis in a mouse model. Intraperitoneal (i.p.) injection of lunasin (4 mg/kg bw/day) reduced the number of liver metastasis by 50% (P = 0.047) and the liver weight/body weight ratio by 23% (P = 0.039). Oral administration of lunasin reduced the number of liver metastasis by 56% (8 mg/kg bw/day, P = 0.293) and 94% (20 mg/kg bw/day, P = 0.247). Immuno- histochemical staining of the liver-tissue section showed that lunasin at 20 mg/kg bw dose did not significantly reduce the expression of proliferating cell nuclear antigen, increased the expression of proapoptotic Bax by 2.7-fold but also increased the expression of the antiapoptotic Bcl-2 by 3.8-fold. Regarding epigenetic markers, H3K18 was not signifi-cantly affected by either oral dose while H4K8 was dose dependently increased by 2.3-fold (P = 0.001, 8 mg/kg bw) and 2.7-fold (P < 0.001, 20 mg/kg bw). On the other hand, i.p. injection of lunasin reduced both histone acetylation markers significantly. The difference on the effects can be attributed to the different routes of administration used lead-ing to digestion of lunasin when given by oral gavage. In conclusion, lunasin reduced colon cancer metastasis in vivo; however, more studies are needed to determine the oral dose of lunasin and prevent colon cancer metastasis.