Amentoflavone promotes ferroptosis by regulating reactive oxygen species (ROS) /5’AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) to inhibit the malignant progression of endometrial carcinoma cells

Abstract

It was reported that amentoflavone (AF) had anti-tumor ability. Therefore, this study aimed to investigate the role of AF in endometrial cancer as well as to discuss its underlying mechanism. The viability, proliferation, and apoptosis of endometrial carcinoma cells (KLE) with AF administration were detected by methyl tetrazolium (MTT) assay, clone formation, and terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assays. Thiobarbituric acid reactive substance (TBARS) production and Fe 2+ level in AF-treated KLE cells were detected by TBARS assay and Iron assay. The expressions of proliferation- apoptosis-, ferroptosis-, and 5'AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling-related proteins in AF-treated KLE cells were detected by western blot analysis. Reactive oxygen species (ROS) expression in AF-treated KLE cells was determined by ROS assay kit. N-acetyl cysteine (NAC), which is an inhibitor of ROS, was used to confirm whether AF exerted its effects on KLE cells through ROS/AMPK/mTOR signaling. As a result, AF inhibited the viability and proliferation of KLE cells but promoted apoptosis and ferroptosis. The expressions of ROS and AMPK were increased, while mTOR expression was decreased in AF-treated KLE cells. NAC reversed the effects of AF on biological behaviors of KLE cells by inactivating ROS/AMPK/mTOR signaling. In conclusion, AF promoted ferroptosis by activating ROS/AMPK/mTOR to inhibit the viability and proliferation and promoted the apoptosis and ferroptosis of KLE cells.

Ferroptosis-related lncRNA model based on CFAP58-DT for predicting prognosis and immunocytes infiltration in endometrial cancer

“…Ferroptosis is involved in a series of cancer processes, including diagnosis, prognosis, carcinogenesis, cancer resistance, and treatment of hepatocellular carcinoma (8)(9)(10), renal cell carcinoma (11)(12)(13), glioma (14)(15)(16), ovarian cancer (17)(18)(19), and so on. Furthermore, drugs such as quercetin, simvastatin and amentoflavone, as well as genes including CircRAPGEF5, protein tyrosine phosphatase non-receptor type 18 (PTPN18) and tyrosine kinase (ELK1) Oncogene participated in regulation of ferroptosis and thus played a role in EC (20)(21)(22)(23)(24)(25)(26). What's more, ferroptosis plays an important role in anti-tumor immunity.…”

Beyond Mortality: Exploring the Influence of Plant Phenolics on Modulating Ferroptosis—A Systematic Review

“…This modulation resulted in the accumulation of iron, overproduction of ROS, and cell death through ferroptosis [ 10 , 51 , 58 , 59 , 60 , 61 ]. Furthermore, amentoflavone [ 62 , 63 , 64 ], baicalin [ 54 , 55 , 65 ], erianin [ 37 , 41 , 57 , 66 , 67 ], gambogenic acid [ 68 ], auriculasin [ 69 ], wogonin [ 70 ], quercetin [ 71 , 72 ], shikonin [ 73 , 74 ], scoparone [ 75 ], osthole [ 76 ], also have shown to be able to inhibit cancer growth though the induction of ferroptosis. All of this suggests the potential for developing novel cancer treatments grounded in natural products acting as ferroptosis inducers.…”

Quercetin Suppresses Ferroptosis in Chondrocytes via Activating the Nrf2/ GPX4 Signaling Pathway

“…13,41 Ferroptosis is primarily driven by lipid peroxidation, with an excess of lipid ROS being considered as a characteristic feature of this process. 42 So, in this study, a ferroptosis model in chondrocytes was established using RSL3 stimulation to simulate the process of ferroptosis. Given the critical role of ferroptosis in chondrocytes in the pathogenesis of OA, finding suitable intervention drugs is urgently needed.…”