Curcumin relieves the arecoline-induced fibrosis of oral mucosal fibroblasts via inhibiting HIF-1α/TGF-β/CTGF signaling pathway: an in vitro study

Oral submacosal fibrosis (OSF) has been recognized as one of the oral potentially malignant disorders. Areca nut chewing is implicated in this pathological fibrosis. The current treatments for OSF have failed to achieve the desired curative effect. Here, we propose that curcumin has excellent therapeutic effect on OSF and explore its specific mechanism. Transwell assay was performed to detected cell migration. Flow cytometry was used to measured apoptosis. And MTT assay was performed to test cell viability. Gene and protein levels were detected by quantitative real-time polymerase chain reaction (qPCR) and western blotting. Our results displayed that curcumin treatment reduced fibrosis-related molecules (collagen type I alpha 1, collagen type III alpha 1, tissue inhibitor of metalloprotease 2) in arecoline-treated oral mucosal fibroblasts and elevated matrix metalloproteinase 2 expression. Additionally, curcumin could suppress cell proliferation and migration, and enhance the apoptosis of arecoline-treated normal oral mucosal fibroblasts. Most importantly, the hypoxia-inducible factor-1α (HIF-1α), transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) expressions in arecoline-treated normal oral mucosal fibroblasts were reduced after exposure to curcumin, whereas the activation of HIF-1α/TGF-β/CTGF axis reversed curcumin's effect on improving fibrosis of arecoline-treated normal oral mucosal fibroblasts. Therefore, curcumin alleviated oral submucosal fibrosis via inhibiting HIF-1α/TGF-β/CTGF axis. In summary, curcumin effectively inhibited the migration and proliferation and promoted apoptosis in arecoline-induced normal oral mucosal fibroblasts by inactivating HIF-1α/TGF-β/CTGF pathway. And curcumin might be a potential therapeutic drug for OSF treatment.