The risk of cancer increases with aging due to the accumulation of cellular deterioration that can spread to other organs through the blood and lymphatic vessels. Therefore, the inhibition of metastasis is a major concern for the treatment of cancer. Several synthetic drugs have been developed for the treatment of various cancers. However, these drugs are effective; nonspecific action and side effects on the normal human cells limit their wide acceptance, thus demanding some potential alternative. Hence, the present study emphasizes investigating the effect of a methanolic extract of Agrimonia Pilosa (APLME) on matrix metalloproteinases (MMPs) in human fibroblast sarcoma cells. The action of APLME on MMP-2 and MMP-9 was investigated using gelatin zymography. APLME suppressed the activities of MMP-2 and MMP-9 in PMA (phorbol myristate acetate)-treated HT1080 cells. In addition, western blot analysis and immunofluorescence were performed to investigate the effect of APLME on the expression of the proteins that are the major proteins involved in cell invasion and metastasis. APLME treatment inhibited the expression of MMP-2 and MMP-9 in addition to the activations of JNK, ERK, and AKT-1. Furthermore, APLME was observed to suppress cell invasion related to metastasis using cell invasion assay. Therefore, the above findings indicate that APLME inhibits the expression activity of MMP-2 and MMP-9 via inactivation of ERK and JNK in addition to AKT-1, leading to inhibiting cell invasion. Therefore, these results indicate that APLME may be used as a candidate substance for inhibiting cell invasion. PRACTICAL APPLICATIONS: Cancer increases the cell invasion to other organs through the blood and lymphatic vessels. Cancer cells deplete the nutrients and create new blood vessels that infiltrate and metastasize to other tissues. Therefore, this present study examined the effect of Agrimonia Pilosa on cell invasion. It was found that Agrimonia Pilosa methanolic extract inhibited the invasion of cancer cells through the inactivation of ERK and JNK. In addition, APLME reduced the activation and protein expression of MMP-2 and MMP-9 in addition to AKT-1. Thus, APLME can be utilized as a potential alternative therapeutic agent for inhibiting metastasis.
Keywords: Agrimonia Pilosa; MMP-2; MMP-9; cell invasion; metastasis.
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