ß-Asarone suppresses TGF-ß/Smad signaling to reduce the invasive properties in esophageal squamous cancer cells.

Esophageal cancer is one of the most common malignancies which induces cancer-related death. Cancer metastasis and recurrence are the main obstacle faced in esophageal cancer treatment. ß-Asarone has been shown to act as an anti-cancer reagent in various cancer types. However, the anti-cancer activities of ß-Asarone in esophageal cancer have not been shown. In the current study, we show that ß-Asarone suppressed the proliferation of esophageal squamous cancer cells (ESCC) in both dose- and time-dependent manners. Moreover, ß-Asarone treatment increases activated caspase 3, caspase 9, and cleaved poly ADP-ribose polymerase, and induces apoptosis in ESCC. Additionally, ß-Asarone also suppresses epithelial-mesenchymal transition (EMT) and the invasive and migratory abilities in ESCC. Interestingly, ß-Asarone suppresses TGF-ß/Smad signaling by inhibition of TGF-ß-induced phosphorylation of Smad2 and Smad3. Importantly, we show that inhibition of TGF-ß/Smad signaling activation is critical for ß-Asarone-suppressed EMT. Our data revealed a novel role of ß-Asarone which targets invasive properties by inhibiting TGF-ß/Smad signaling activation in ESCC. Our study suggests the potential application of ß-Asarone to reduce cancer metastasis and recurrence in esophageal cancer treatment.

MiR-181 Enhances Proliferative and Migratory Potentials of Retinal Endothelial Cells in Diabetic Retinopathy by Targeting KLF6.

PURPOSE: We aimed to uncover the role of microRNA-181 (miR-181) in the disease onset of diabetic retinopathy (DR) and its underlying mechanism. METHODS: MiR-181 levels in plasma and aqueous humor samples of non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR) and healthy subjects were analyzed by microarray and quantitative real-time polymerase chain reaction (qRT-PCR). Proliferative and migrative capacities of human retinal endothelial cells (hRECs) regulated by miR-181 were assessed. The binding between miR-181 and Kruppel-like factor 6 (KLF6) was verified by dual-luciferase reporter assay. RESULTS: MiR-181 was upregulated in plasma and aqueous humor samples of NPDR and PDR patients. Overexpression of miR-181 stimulated hRECs to proliferate and migrate. KLF6 was the downstream gene binding miR-181, which was involved in the regulation of hRECs by miR-181. CONCLUSIONS: MiR-181 is upregulated in plasma and aqueous humor of DR patients. It enhances proliferative and migratory potentials of retinal endothelial cells by targeting KLF6.