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

Abstract

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.

Baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ROS to inhibit PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways

“…However, our work did not focus on intercellular Ca 2+ in autophagy or the associated signaling pathways. An abundance of data indicates that the PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways are closely related to proliferation, apoptosis and autophagy [70] , [71] , [72] . In addition, extensive studies have reported that accumulating ROS inhibits the PI3K/Akt/mTOR, ERK1/2 and β-catenin pathways, leading to autophagy and apoptosis [36] , [37] , [73] .…”

Streptococcus lutetiensis Induces Autophagy via Oxidative Stress in Bovine Mammary Epithelial Cells

“…Furthermore, HO-1 and NQO-1 proteins in MAC-T cells were elevated after S. lutetiensis infection. Recent research demonstrated that NAC could block ROS production and further reversed LC3 II accumulation which triggered by coenzyme Q 0 , and the same mechanism of NAC also occurred in chrysin-induced autophagy [ 50 , 51 ]. We used NAC, an efficient ROS inhibitor [ 52 , 53 ].…”

The Role of m6A RNA Methylation in Cancer: Implication for Nature Products Anti-Cancer Research

“…Several recent studies have reported that chrysin exerts its anti-cancer effects on endometrial cancer, gastric cancer, breast, lung, cervical, bladder, breast cancer, and colorectal cancer, etc. via selectively inhibiting various cell signaling pathways, such as: Akt/mTOR, JNK1/2, ERK1/2, NF-κB, etc., and promoting tumor cells apoptosis and autophagy ( Xia et al, 2015a ; Xia et al, 2015b ; Roy et al, 2019 ; He et al, 2021 ). However, the regulatory relationship between chrysin and m6A enzyme has not been reported.…”