DMC-HA, a novel HDAC inhibitor, has previously demonstrated antiproliferative activity against various cancers, including gliomas. However, the role of DMC-HA in the regulation of EMT and its underlying mechanisms remain unknown. This study aimed to explore the effects of DMC-HA on TGF-β1-induced EMT in human gliomas and the underlying mechanisms involved. Our results showed that TGF-β1 induced EMT of U87 and U251 cells, leading to a decrease in epithelial marker ZO-1 and an increase in mesenchymal markers N-cadherin and Vimentin. Moreover, TGF-β1 treatment resulted in a significant increase in the migratory and invasive abilities of the cells. However, treatment with DMC-HA effectively inhibited the augmented migration and invasion of glioma cells induced by TGF-β1. Additionally, DMC-HA inhibits TGF-β1-induced EMT by suppressing canonical Smad pathway and non-canonical TGF-β/Akt and Erk signalling pathways. These findings suggest that DMC-HA has potential therapeutic implications for gliomas by inhibiting EMT progression.
Keywords: DMC-HA; HDACs; TGF-β1; epithelial-mesenchymal transition; gliomas.