[No authors listed]
Formononetin (Form), a phytoestrogen extracted from the roots of Astragalus membranaceus, is one of the fundamental herbs used in traditional Chinese medicine because of its protective effects against certain malignant tumors. However, its role in colon carcinoma cells and the underlying molecular mechanisms have not been completely elucidated. The present study aimed to demonstrate that Form significantly inhibited the proliferation and invasion of the colon carcinoma cell lines SW1116 and HCT116. Mechanistic studies have suggested that Form suppresses colon carcinoma cell growth by downregulating cell cycleâassociated protein (cyclin D1) expression and arresting the cell cycle at the G0âG1 checkpoint. Further studies revealed that treatment with Form inhibits matrix metalloproteinase (MMP)2 and MMP9 expression. Aditionally, the results demonstrated that Form significantly increased microRNA (miR)â149 expression. Following miRâ149 overexpression in SW1116 and HCT116 cells using an miRâ149 mimic, cell viability and Ephrin typeâB receptor 3 (EphB3) levels decreased. Furthermore, the inhibitory effects of Form were associated with phosphatidylinositol 3âkinase (PI3K)/protein kinase B (AKT) and signal transducer and activator of transcription 3 signaling pathways. These results indicated the suppressive effect of Form on colon carcinoma cell proliferation and invasion, possibly via miRâ149âinduced EphB3 downregulation and the inhibition of the PI3K/AKT and signaling pathways. Overall, Form may be used as a novel candidate for the clinical treatment of colorectal cancer in the future.
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