Diosmin Enhances the Anti-migration Activity of Curcumin Analog PGV-1 on Colorectal Cancer Cells

BACKGROUND: Diosmin enhances the cytotoxicity of Pentagamavunone-1 (PGV-1) in cancer cells. PGV-1 and diosmin are predicted to target several matrix metalloproteinases (MMPs) in metastatic cancer, including colorectal cancer, but the antimigration potency of their combination has not established yet. This study evaluates the anti -migration effect of PGV-1 and diosmin combination in colorectal cancer. METHODS: The cytotoxicity assay using Cell Counting Kit 8 (CCK-8) method in WiDr colorectal cancer cells was carried out to determine the concentration for antimigration experiments. The wound healing assay was used to observe the anti -migration activity by measuring the cellfree area. Gelatin zymography was employed to detect the MMP activity indicating by the clear band density. The interaction between PGV-1 or diosmin and MMP proteins was predicted by molecular dockings. RESULTS: PGV-1 was cytotoxic (IC50 17 mu M), while diosmin up to 100 mu M did not affect cell viability. Both 10 mu M PGV-1 as well as 50 and 100 mu M diosmin slowed down the closure of cell -free area. A 100 mu M diosmin was significantly enhance the anti -migratory activity of 50 and 100 mu M PGV-1. The activity of MMP-9 and MMP-2 was also lower in the presence of diosmin compared to than that of PGV-1 alone. PGV-1 or diosmin was also able to interact with MMP proteins with a lower energy compared to than that of the native ligands. CONCLUSION: Diosmin enhances the anti -migration activity of PGV-1 in WiDr cells, possibly by affecting MMPs' activity. This study is an evidence that diosmin is a potential co -chemotherapy candidate for PGV-1, that can be utilized to overcome metastatis in colorectal cancer.