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

Content Provider	Europe PMC
Author	He, Yu Shi, Yuchuan Yang, Yang Huang, Huanhuan Feng, Yifan Wang, Yunmeng Zhan, Lei Wei, Bing
Copyright Year	2021
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.
ISSN	11073756
Journal	International Journal of Molecular Medicine
Volume Number	48
PubMed Central reference number	PMC8285048
Issue Number	3
PubMed reference number	34278450
e-ISSN	1791244X
DOI	10.3892/ijmm.2021.5005
Language	English
Publisher	D.A. Spandidos
Publisher Date	2021-07-19
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © He et al.
Subject Keyword	endometrial cancer chrysin autophagy apoptosis reactive oxygen species Akt/mTOR
Content Type	Text
Resource Type	Article
Subject	Genetics Medicine