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Updated: Jul 15, 2025
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Published on: March 15, 2024
Metformin induces ferroptosis through the Nrf2/HO-1 signaling in lung cancer
Chengmin Deng1, Lin Xiong2, Yang Chen1,3
1Scientific Research Center, The First People's Hospital of Zunyi (The Third Affiliated Hospital of Zunyi Medical University), Zunyi, Guizhou, China.
Background:
Metformin is the most frequently prescribed medication for the treatment of type II diabetes mellitus and has played an anti-tumor potential in a variety of cancer types. Metformin can inhibit the growth of many cancer cells through various mechanisms, including ferroptosis. However, it is still unclear whether metformin can induce ferroptosis in lung cancer.
Methods:
This study evaluated the anti-tumor effect of metformin by detecting the levels of oxidative stress factors, the levels of ferrous ions, and the expression of ferroptosis-related genes in A549 and H1299 lung cancer cell lines treated with or without metformin.
Results:
The results showed that metformin treatment increased the levels of MDA, ROS and iron ions, while decreased the levels of GSH, T-SOD and CAT. Meanwhile, metformin treatment reduced the protein expression levels of Gpx4 and SLC7A11, Nrf2 and HO-1, while the addition of ferroptosis inhibitor ferrostatin-1 reversed the reduction.
Conclusions:
These results demonstrated that metformin exerts anti-tumor effects by inducing ferroptosis through the Nrf2/HO-1 signaling pathway in lung cancer cells, providing a theoretical basis for drug therapy of lung cancer patients.
Insights
Metformin induces ferroptosis, a cell death process, in lung cancer cells. This anti-tumor effect is mediated by the Nrf2/HO-1 pathway, offering potential new treatments for lung cancer.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Metformin, a common type II diabetes drug, shows anti-tumor potential in various cancers.
- Metformin inhibits cancer cell growth via mechanisms including ferroptosis.
- Its role in inducing ferroptosis in lung cancer remains unclear.
Purpose of the Study:
- To investigate the anti-tumor effects of metformin in lung cancer.
- To determine if metformin can induce ferroptosis in lung cancer cells.
- To elucidate the molecular pathways involved in metformin-induced ferroptosis.
Main Methods:
- Lung cancer cell lines (A549, H1299) were treated with metformin.
- Levels of oxidative stress factors (MDA, ROS, GSH, T-SOD, CAT) and iron ions were measured.
- Expression of ferroptosis-related genes (Gpx4, SLC7A11, Nrf2, HO-1) was analyzed.
Main Results:
- Metformin increased MDA, ROS, and iron ion levels, while decreasing GSH, T-SOD, and CAT.
- Metformin reduced Gpx4, SLC7A11, Nrf2, and HO-1 protein expression.
- Ferrostatin-1, a ferroptosis inhibitor, reversed these metformin-induced changes.
Conclusions:
- Metformin induces ferroptosis in lung cancer cells.
- The Nrf2/HO-1 signaling pathway mediates metformin's anti-tumor effects.
- These findings support metformin as a potential therapeutic agent for lung cancer.
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