Metformin Unveils New Discovery: Promoting Tumor Cell Death
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Metformin Unveils New Discovery: Enhancing Cancer Patients’ Anti-Tumor Immunity and Promoting Tumor Cell Death.
Metformin, while serving various purposes, should still be used under medical guidance and in a judicious manner.
Metformin, a widely used prescription drug with over a hundred million people taking it worldwide, is renowned for its primary role in lowering blood glucose levels by inhibiting liver glucose production. It is a first-line treatment for type 2 diabetes and stands as one of the most prescribed medications globally.
Despite being an old drug, research into Metformin has never ceased, with its popularity steadily rising. Metformin continues to surprise us by revealing its various benefits beyond glucose control, including weight loss. Numerous pre-clinical and clinical studies have observed its positive effects in areas such as anti-aging, treating cognitive disorders, and addressing cardiovascular diseases, earning it the moniker “miracle drug.”
Recent research findings suggest that Metformin may enhance anti-tumor immune responses. However, the underlying immunological mechanisms have remained unclear until now.
Recently, researchers from Okayama University in Japan published a study titled “Mitochondrial reactive oxygen species trigger metformin-dependent antitumor immunity via activation of Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8+ T lymphocytes” in the Journal for ImmunoTherapy of Cancer.
The study discovered that Metformin can activate the proliferation of tumor-infiltrating CD8+ T lymphocytes (CD8TIL), which are immune cells known for their anti-tumor functions. It also promotes the secretion of interferon-gamma (IFN-γ) by these cells, altering the tumor microenvironment to facilitate the death of tumor cells. These findings strongly suggest the potential of using Metformin as a medication to enhance cancer patients’ anti-tumor immunity.
The lead author of the study, Professor Heiichiro Udono, had contemplated giving up cancer research after his father’s cancer-related death. However, inspiration struck him during a cancer and hypoxia seminar. He realized that previous research often overlooked the Warburg effect, a metabolic characteristic unique to cancer cells, where they exhibit heightened glycolysis even in the presence of ample oxygen.
The Warburg effect fuels cancer growth, and restoring normal metabolism in cancer by reversing this effect could aid in cancer treatment. During the seminar, he also learned about Metformin’s potential in cancer immunotherapy and connected the dots.
Professor Udono and his team conducted a series of experiments involving cancer cell lines and knockout mouse models to identify potential biomolecules responsible for Metformin-dependent anti-tumor immunity. They explored the intracellular mechanisms of CD8TIL exposed to Metformin and assessed various biomarkers. Given that CD8TIL produce interferon to attack cancer cells, they also evaluated interferon levels.
The research team found that Metformin induces the production of reactive oxygen species (ROS) in the mitochondria of CD8TIL, enhancing glycolysis. These ROS activate the growth of CD8TIL, thereby promoting the proliferation of these anti-tumor immune cells. This promoting effect is mediated through the transcription factor Nrf, which participates in antioxidant stress responses.
Additionally, the research team ruled out cell apoptosis as the mechanism behind Metformin’s anti-tumor effect. Metformin also leads to the robust secretion of interferon-gamma by CD8TIL, thereby altering the tumor microenvironment to promote the death of tumor cells.
Metformin Unveils New Discovery: Promoting Tumor Cell Death
(source:internet, reference only)
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