Acacetin Promotes Cell Death and Inhibits Migration in Follicular Thyroid Cells

Background/Aim: Distant metastasis and chemoresistance render the prognosis of follicular thyroid cancer (FTC) unsatisfactory. Acacetin, which is found in various traditional Chinese medicinal herbs, has been reported to exert antitumor effects. Herein, the molecular mechanisms of acacetin on the proliferation of FTC WRO cells were demonstrated. Materials and Methods: Network pharmacology analysis was performed to determine the target genes of acacetin. MTT assay and flow cytometry analyses were conducted to detect cell death. Migration was detected by wound healing assay. Western blot analysis was performed to detect protein expression. Results: Acacetin dose-dependently repressed the viability of WRO cells. Flow cytometry analysis revealed that acacetin promoted apoptosis in WRO cells. Acacetin clearly increased cleavage of caspase-3 and PARP, decreased Bcl2 expression and attenuated AKT and ERK phosphorylation. Acacetin increased acidic vesicular staining and autophagy-related protein expression of WRO cells, as shown by acridine orange staining and significantly increased the expression levels of phosphorylated p62, p62, and LC3 II. In addition, treatment with sublethal doses (0, 3, 6, and 12.5 μM) of acacetin significantly mitigated the migration of WRO cells, as evidenced by wound healing assay. Zymography analysis revealed that acacetin downregulated matrix metalloproteinase (MMP)-9 activities. Acacetin also repressed the expression levels of MMP-9 and mesenchymal markers such as Snail and increased the expression of epithelial markers such as E-cadherin. Conclusion: Acacetin promoted cell death through apoptosis. As no autophagic-flux assay was performed, our findings should be limited to increased acidic vesicular staining and accumulation of LC3-II, p62, and phosphorylated p62. Moreover, acacetin significantly repressed migration in FTC cells by reversing epithelial-to-mesenchymal transition. Collectively, our findings suggested that acacetin could be a potential anti-FTC agent.