Epigallocatechin-3-gallate attenuates fluoride induced apoptosis via PI3K/FoxO1 pathway in ameloblast-like cells

Fluoride is a double-edged sword. It was widely used for early caries prevention while excessive intake caused a toxicology effect, affected enamel development, and resulted in dental fluorosis. The study aimed to evaluate the protective effect and mechanism of Epigallocatechin-3-gallate (EGCG) on the apoptosis induced by fluoride in ameloblast-like cells. We observed that NaF triggered apoptotic alterations in cell morphology, excessive NaF arrested cell cycle at the G1, and induced apoptosis by up-regulating Bax and down-regulating Bcl-2. NaF activated the insulin-like growth factor receptor (IGFR), and phosphatidylinositol-3-hydroxylase (p-PI3K), while dose-dependently down-regulating the expression of Forkhead box O1 (FoxO1). EGCG supplements reversed the changes in LS8 morphology, the cell cycle, and apoptosis induced by fluoride. These results indicated that EGCG possesses a protective effect against fluoride toxicity. Furthermore, EGCG suppressed the activation of p-PI3K and the down-regulation of FoxO1 caused by fluoride. Collectively, our findings suggested that EGCG attenuated fluoride-induced apoptosis by inhibiting the PI3K/FoxO1 signaling pathway. EGCG may serve as a new alternative method for dental fluorosis prevention, control, and treatment. NaF activated PI3K phosphorylation level, promoted FoxO1 transporting to the cytoplasm, decreased nuclear FoxO1, reduced Bcl-2/Bax, and induced apoptosis in LS8. EGCG inhibited PI3K phosphorylation activation, sustained nuclear FoxO1 levels, and decreased the apoptosis rate induced by fluoride in LS8. Therefore, EGCG may have potential as a future therapeutic for dental fluorosis. [Display omitted] •Fluoride induces ameloblast apoptosis by reducing cell anti-apoptosis ability.•Epigallocatechin-3-gallate plays a protective effect in fluoride pollution.•Epigallocatechin-3-gallate alleviates fluoride-induced apoptosis via PI3K/FoxO1pathway.