Triptolide Promotes Ferroptosis in Cervical Cancer Cell via NRF2/xCT/GPX4

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Cervical cancer (CC) poses a significant threat to women's health.
• Developing less toxic and more effective CC therapies is crucial.
• Triptolide (Tri), from Tripterygium Wilford, exhibits antitumor properties.

Purpose of the Study:

• To investigate if Triptolide (Tri) induces ferroptosis in cervical cancer (CC) cells.
• To elucidate the underlying molecular mechanism of Tri-induced ferroptosis in CC.
• To evaluate the therapeutic potential of Tri in CC models.

Main Methods:

• In vitro: CC cells treated with Tri; assessed lipid peroxidation (flow cytometry, immunofluorescence).
• Explored molecular mechanisms via Western blot; verified NRF2/GPX4/xCT axis regulation.
• In vivo: Tumor-bearing mice models used to assess Tri's effect on tumor growth.

Main Results:

• Tri inhibited CC cell growth and migration in vitro.
• Tri significantly enhanced ferroptosis by increasing lipid peroxidation.
• Tri reduced NRF2 expression, consequently repressing GPX4 and xCT.
• NRF2 overexpression reversed Tri's effects on ferroptosis.
• Tri markedly inhibited tumor growth in vivo by targeting the NRF2/GPX4/xCT axis.

Conclusions:

• Triptolide (Tri) exerts antitumor effects against cervical cancer (CC) by inducing ferroptosis.
• The mechanism involves the inhibition of the NRF2/GPX4/xCT signaling pathway.
• Tri represents a promising therapeutic agent for cervical cancer treatment.