Chrysin induces autophagy through the inactivation of the ROS-mediated Akt/mTOR signaling pathway in endometrial cancer

Endometrial cancer (EC) is widely known as an aggressive malignancy. Due to the limited therapeutic options and poor prognosis of patients with advanced-stage EC, there is a need to identify effective alternative treatments. Chrysin is a naturally active flavonoid (5,7-dihydroxyflavone), which has been demonstrated to exert anticancer effects and may present a novel strategy for EC treatment. However, the role of chrysin in EC remains largely unclear. The aim of the present study was to examine the anticancer effects of chrysin on EC. The results revealed that, in addition to apoptosis, chrysin increased the LC3II expression levels and markedly accelerated the autophagic flux, suggesting that chrysin induced both the autophagy and apoptosis of EC cells. Furthermore, the inhibition of autophagy by chloroquine enhanced the inhibitory effect on cell proliferation and the promotion of the chrysin-induced apoptosis of EC cells, indicating that chrysin-induced autophagy was a cytoprotective mechanism. Additionally, chrysin led to the production of intracellular reactive oxygen species (ROS). N-acetylcysteine (NAC) pretreatment significantly inhibited chrysin-induced autophagy, suggesting that ROS activated autophagy induced by chrysin in EC cells. Furthermore, the phosphorylated (p-) Akt and p-mTOR levels were significantly decreased in a concentration-dependent manner following treatment with chrysin, while NAC blocked these effects. Taken together, these findings demonstrated that chrysin-induced autophagy via the inactivation of the ROS-mediated Akt/mTOR signaling pathway in EC cells.

Automated summary

Chrysin shows potential therapeutic effects on EC by inducing both cell autophagy and apoptosis to inhibit cell proliferation and promote cell death. Additionally, chrysin induces intracellular ROS production, leading to autophagy activation. The study revealed that chrysin-induced autophagy in EC cells is mediated through the inhibition of the ROS-mediated Akt/mTOR signaling pathway.