The effect of lunasin on
colon cancer metastasis was studied using three human
colon cancer cell lines in vitro and a liver
metastasis model of
colon cancer in vivo. Lunasin bound with α5β1
integrin and internalized into the nucleus of KM12L4 human
colon cancer cells. Lunasin (10 μM) inhibited the activation of
focal adhesion kinase (FAK) by 28%, 39% and 60% in RKO, HCT-116 and KM12L4 human
colon cancer cells, respectively. Lunasin caused an increase in the expression of the inhibitor of kappa B alpha (IκB-α), a decrease in nuclear p50 NF-κB and a reduction in the migration of
cancer cells. Lunasin (4 mg/kg bw) inhibited
metastasis and potentiated the effect of
oxaliplatin by reducing the expression of
proliferating cell nuclear antigen. Liver metastatic nodules were reduced from 28 (PBS) to 14 (lunasin, P = 0.047) while combination of lunasin and
oxaliplatin to 5 (P = 0.004). The
tumor burden was reduced from 0.13 (PBS) to 0.10 (lunasin, P = 0.039) to 0.04 (lunasin +
oxaliplatin, P < 0.0001). Moreover, lunasin potentiated the effect of
oxaliplatin in modifying expression of
proteins involved in apoptosis and
metastasis including Bax, Bcl-2, IKK-α and p-p65. Lunasin inhibited
metastasis of human
colon cancer cells by direct binding with α5β1
integrin suppressing FAK/ERK/NF-κB signaling, and potentiated the effect of
oxaliplatin in preventing the outgrowth of
metastasis.