Puerarin inhibits thyroid cancer cell survival and enhances autophagy by regulating the FOXO1/GABARAPL1 signaling pathway.

Puerarin, a naturally occurring isoflavone, exhibits extensive pharmacological properties. Accumulating studies have validated its antitumor effects in several types of cancer. However, whether puerarin regulates autophagy in thyroid cancer and the underlying molecular cascade remain unelucidated. Herein, we aimed to explore the in vitro impacts of puerarin on autophagy in thyroid cancer cells and its related molecular mechanisms. Our findings indicated that puerarin attenuated cellular viability while augmenting both apoptotic and autophagic responses in thyroid cancer cell lines. Mechanistically, puerarin upregulated FOXO1 in these cells. FOXO1 knockdown abrogated puerarin-mediated suppression of cell survival and induction of autophagy. Additionally, GABARAPL1 functioned as a downstream effector of FOXO1, mediating FOXO1's biological roles in puerarin-exposed thyroid cancer cells. Collectively, these data establish that puerarin manifests antineoplastic activity in thyroid carcinoma by curtailing cell survival and potentiating autophagy via modulation of the FOXO1/GABARAPL1 axis. This study offers novel mechanistic clues for exploring puerarin as a potential therapeutic candidate against thyroid cancer.