Telmisartan Inhibits Non-Small Cell Lung Cancer by Inducing Ferroptosis through the NRF2/GPX4 Signaling Axis

Area of Science:

• Oncology
• Molecular Biology
• Cell Death Research

Background:

• Drug resistance poses a significant challenge in Non-Small Cell Lung Cancer (NSCLC) treatment.
• Telmisartan, an antihypertensive drug, exhibits anti-tumor properties, but its mechanism is not fully understood.
• Ferroptosis, a distinct form of regulated cell death, represents a potential therapeutic target in cancer.

Purpose of the Study:

• To determine if telmisartan inhibits NSCLC by inducing ferroptosis.
• To elucidate the molecular mechanism by which telmisartan affects NSCLC, focusing on ferroptosis.

Main Methods:

• In vitro cell assays and in vivo mouse models were employed.
• Molecular biology techniques were utilized to investigate telmisartan's mechanism of action.
• The role of ferroptosis was assessed using ferroptosis inhibitors.

Main Results:

• Telmisartan demonstrated significant suppression of NSCLC cell proliferation and tumor growth in both in vitro and in vivo settings.
• Telmisartan induced ferroptosis by inhibiting the nuclear translocation of Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) and reducing Glutathione Peroxidase 4 (GPX4) expression.
• The anti-tumor effects of telmisartan were observably reversed upon the administration of ferroptosis inhibitors.

Conclusions:

• Telmisartan effectively inhibits NSCLC proliferation and induces ferroptosis through the NRF2/GPX4 signaling pathway.
• The findings suggest telmisartan's potential as a novel therapeutic strategy for NSCLC treatment.
• Telmisartan's mechanism involves modulating NRF2 nuclear translocation, impacting GPX4 expression and inducing ferroptosis in NSCLC.