Verticinone inhibits cell growth and induces pyroptosis via regulating AKT pathway in papillary thyroid cancer.

BACKGROUND

Verticinone, an alkaloid isolated from Fritillaria, exhibits a range of biological activities. This study aims to investigate the effects of verticinone on papillary thyroid carcinoma (PTC), the most prevalent histological type of thyroid cancer, as well as the potential mechanisms underlying these effects.

METHODS

Cell counting kit-8, colony formation assay, and 5-ethynyl-2'-deoxyuridine staining were employed to evaluate the impact of verticinone on the proliferation capacity of PTC cells. Wound healing and Transwell assays were conducted to assess the effects of verticinone on the migration and invasion abilities of PTC cells. Flow cytometry was utilized to detect apoptosis in PTC cells. Western blot analysis was performed to measure the expression levels of relevant proteins. Additionally, network pharmacology analysis was conducted to identify potential targets of verticinone and thyroid carcinoma, and molecular docking was used to elucidate the targeting relationship. Finally, the effect of verticinone on tumor growth was evaluated using a xenograft tumor model.

RESULTS

Verticinone inhibited the proliferation, migration, and invasion, and induced apoptosis and pyroptosis of PTC cells in a dose-dependent manner. Mechanically, verticinone targeted and inhibited protein kinase B (AKT), facilitating its degradation. AKT overexpression significantly eliminated the effect of verticinone on biological behavior of PTC cells. The results of xenograft tumor experiments demonstrated the inhibitory effect of verticinone on PTC tumor growth.

CONCLUSION

Verticinone inhibited the growth of PTC cells and induced pyroptosis by regulating the AKT pathway.