Vitamin B2 is essential for human health, but new research suggests it may help cancer cells survive.
Vitamin B2, also known as riboflavin, cannot be produced by the body and must be obtained from food sources such as dairy products, eggs, meat, and green vegetables. Once absorbed, vitamins are converted into molecules that protect cells from oxidative damage and support other important biological functions.
Scientists at the Rudolf Virchow Center (RVZ) at Julius-Maximilians-Universität Würzburg (JMU) have discovered that this protective effect may have a serious drawback. Their findings show that vitamin B2 metabolism can also prevent the destruction of cancer cells.
“Vitamin B2 plays an important role in protecting cancer cells from ferroptosis, a special form of programmed cell death,” says doctoral student Vera Scafar. She is part of a research team led by José Pedro Friedman Angeli, professor of translational cell biology. This study natural cell biology.
How vitamin B2 helps cancer cells survive
Programmed cell death is one of the body’s natural defense systems. This allows damaged or dangerous cells to be killed in a controlled manner without causing inflammation in nearby tissues. Ferroptosis is one type of this process and is associated with cancer, neurodegenerative diseases, and other serious conditions.
Ferroptosis occurs when iron damage to cell membranes overwhelms the cell’s antioxidant defenses. Cancer cells often avoid this fate by strengthening systems that protect against oxidative stress.
New research has found that vitamin B2 metabolism plays a key role in these defenses. According to the researchers, this means that blocking riboflavin-related pathways could make tumors more vulnerable to ferroptosis and more susceptible to destruction.
Researchers test potential cancer treatment strategies
A protein called FSP1 was at the center of the research team’s work. This protein helps healthy cells avoid unwanted cell death, and vitamin B2 supports its activity.
Using genome editing and cancer cell models, researchers found that cancer cells become much more susceptible to ferroptosis when vitamin B2 is limited.
The researchers believe this process could eventually be used as a cancer treatment by shutting down vitamin B2 metabolism in tumors and causing cancer cell death. However, there are currently no inhibitors specifically designed for that purpose.
To explore this idea further, the researchers tested roseoflavin, a natural compound produced by bacteria that has a structure similar to vitamin B2.
Roseoflavin successfully induces ferroptosis
In laboratory experiments using cancer cell models, researchers found that roseoflavin can induce ferroptosis even at low concentrations.
“We found that roseoflavin causes ferroptosis at low concentrations. Our experiments demonstrate the feasibility of this concept,” said the group leader.
The findings suggest that targeting vitamin B2 metabolism may represent a promising new approach for future ferroptosis-based cancer therapy.
Next, the RVZ research team plans to develop more effective inhibitors of vitamin B2 metabolism and test them in preclinical cancer models.
Potential effects other than cancer
Friedman-Angeli says the importance of ferroptosis extends beyond oncology.
“Ferrotosis is not only associated with cancer; there is growing evidence that ferroptosis also contributes to the pathological processes of neurodegenerative diseases and tissue damage after organ transplantation and ischemia-reperfusion injury.”
Therefore, understanding how vitamin B2 metabolism affects ferroptosis may ultimately help scientists better understand a wide range of diseases that involve excessive or insufficient cell death.
This research was supported by the German Research Foundation (DFG) through the priority program “Ferrotosis: from molecular basics to clinical applications” (SPP2306).
This research was also carried out as part of the DeciFerr (Decoding and Exploitation of Ferroptosis Control Mechanisms in Cancer) project led by Professor Friedman Angeli. Since May 2024, the project has been funded by the European Research Council (ERC) through an ERC Consolidator Grant worth approximately €2 million.
