Triptolide Promotes Ferroptosis in Cervical Cancer Cell via NRF2 / xCT / GPX4
Year: 2024
Type: article
Abstract: Cervical cancer (CC) is a serious risk to women's health; it is necessary to explore less toxic and more effective therapies to cure CC. Triptolide (Tri) is the principal active constituent found in "Tripterygium Wilford," has been shown to have antitumor effects. This study set up to demonstrate whether Tri is capable of inducing ferroptosis in CC cells and its potential mechanism. In vitro, Tri was used to treat CC cells, and lipid peroxidation levels in CC cells were detected by flow cytometry, immunofluorescence, and other experiments; the molecular mechanism of Tri treatment of CC was explored by western blot; moreover, the regulatory effects of Tri on the NRF2/GPX4/xCT axis were verified by overexpressing NRF2 in reverse. In vivo, CC cells tumor-bearing mice were constructed to observe the effect of Tri treatment on tumor growth. In vitro, we have demonstrated that Tri prevents the growth and migration of CC cells. Further investigation revealed that Tri substantially enhances ferroptosis in CC cells by increasing lipid peroxidation accumulation. Mechanically, Tri significantly reduced the expression of NRF2, leading to a corresponding repression of the NRF2 downstream targets GPX4 and xCT. Moreover, overexpressing of NRF2 effectively reversed the impact of Tri on ferroptosis in CC cells. Additionally, animal experiments indicted that Tri markedly inhibited tumor size in nude mice by inhibiting the NRF2/GPX4/xCT axis. Tri exerts antitumor effects by triggering ferroptosis in CC cells through the NRF2/GPX4/xCT axis.
Source: Phytotherapy Research
DOI: 10.1002/ptr.8398
Authors: Miaomiao Feng, Haiwang Wu, Ling Zhu, Jie Gao, Gaopi Deng
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,650
OpenAlex ID: W4405597549