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The inhibitory effect of Agrimonia Pilosa methanolic extract on matrix metalloproteinases in HT1080 cells
1Department of Applied Chemistry & Food Engineering, Dong-Eui University, Busan, Republic of Korea.
Abstract:
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.
Insights
Agrimonia Pilosa methanolic extract (APLME) inhibits cancer cell invasion by suppressing matrix metalloproteinases (MMPs) and key signaling pathways. This natural compound shows potential as an alternative therapeutic agent for inhibiting metastasis.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Cancer metastasis, the spread of cancer cells to distant organs, is a primary cause of cancer-related mortality.
- Aging exacerbates cancer risk through accumulated cellular damage and increased metastatic potential.
- Current synthetic anti-cancer drugs often exhibit nonspecific actions and adverse side effects, necessitating the exploration of alternative therapeutic agents.
Purpose of the Study:
- To investigate the anti-metastatic effects of a methanolic extract of Agrimonia Pilosa (APLME).
- To determine the impact of APLME on matrix metalloproteinases (MMPs), specifically MMP-2 and MMP-9, in human fibroblast sarcoma cells.
- To elucidate the molecular mechanisms underlying APLME's action on cancer cell invasion and metastasis.
Main Methods:
- Gelatin zymography was employed to assess the activity of MMP-2 and MMP-9.
- Western blot analysis and immunofluorescence were utilized to examine protein expression and activation.
- Cell invasion assays were conducted to quantify the effect of APLME on cancer cell migration.
Main Results:
- APLME significantly suppressed the enzymatic activities of MMP-2 and MMP-9 in phorbol myristate acetate (PMA)-treated HT1080 cells.
- APLME treatment led to the inhibition of MMP-2 and MMP-9 protein expression.
- APLME inactivated key signaling pathways, including JNK, ERK, and AKT-1, which are crucial for cell invasion and metastasis.
- APLME demonstrated a marked reduction in cancer cell invasion in vitro.
Conclusions:
- APLME effectively inhibits cancer cell invasion and metastasis by downregulating MMP-2 and MMP-9 expression and activity.
- The anti-metastatic effects of APLME are mediated through the inactivation of the ERK, JNK, and AKT-1 signaling pathways.
- Agrimonia Pilosa methanolic extract represents a promising natural compound for the development of novel anti-metastatic therapeutic strategies.
