Scientists discover vitamin B2 may help cancer cells survive

Also known as riboflavin, vitamin B2 cannot be produced by the body and must come from food sources such as dairy products, eggs, meat, and green vegetables. Once absorbed, the vitamin is converted into molecules that help protect cells from oxidative damage and support other important biological functions.

Scientists at the Rudolf Virchow Centre (RVZ) at Julius-Maximilians-Universität Würzburg (JMU) have now discovered that this protective effect may come with a serious drawback. Their findings show that vitamin B2 metabolism can also shield cancer cells from destruction.

"Vitamin B2 plays a crucial role in protecting cancer cells from ferroptosis, a special form of programmed cell death," says PhD student Vera Skafar. She is part of the research team led by José Pedro Friedmann Angeli, Professor of Translational Cell Biology. The study was published in Nature Cell Biology.

How Vitamin B2 Helps Cancer Cells Survive

Programmed cell death is one of the body's natural defense systems. It allows damaged or dangerous cells to die in a controlled way without triggering inflammation in nearby tissue. Ferroptosis is one type of this process and has been linked to cancer, neurodegenerative diseases, and other serious conditions.

Ferroptosis occurs when iron-driven damage to cell membranes overwhelms a cell's antioxidant defenses. Cancer cells often avoid this fate by strengthening systems that protect them from oxidative stress.

The new study found that vitamin B2 metabolism plays an important role in these protective defenses. According to the researchers, this means that blocking riboflavin-related pathways could make tumors more vulnerable to ferroptosis and easier to destroy.

Researchers Test a Possible Cancer Therapy Strategy

A protein called FSP1 was central to the team's investigation. The protein helps healthy cells avoid unwanted cell death, and vitamin B2 supports its activity.

Using genome editing and cancer cell models, the researchers found that cancer cells became much more sensitive to ferroptosis when vitamin B2 was limited.

The team believes this process could eventually be used as a cancer treatment by shutting down vitamin B2 metabolism in tumors and triggering cancer cell death. However, there is currently no inhibitor specifically designed for that purpose.

To explore the idea further, the researchers tested roseoflavin, a naturally occurring compound produced by bacteria that has a structure similar to vitamin B2.

Roseoflavin Successfully Triggered Ferroptosis

In laboratory experiments using cancer cell models, the researchers found that roseoflavin was able to trigger ferroptosis even at low concentrations.

"It turned out that roseoflavin triggers ferroptosis in low concentrations," says the group leader, "our experiments show the feasibility of this concept."

The findings suggest that targeting vitamin B2 metabolism could become a promising new approach for future cancer therapies based on ferroptosis.

Next, the RVZ research team plans to develop more effective inhibitors of vitamin B2 metabolism and test them in preclinical cancer models.

Potential Implications Beyond Cancer

Friedmann Angeli says the importance of ferroptosis extends beyond oncology.

"Ferroptosis is not only relevant to cancer. Increasing evidence suggests that it also contributes to pathological processes in neurodegenerative diseases and in tissue damage following organ transplantation or ischemia-reperfusion injury."

Because of this, understanding how vitamin B2 metabolism influences ferroptosis could eventually help scientists better understand a wide range of diseases involving excessive or insufficient cell death.

The research was supported by the German Research Foundation (DFG) through the priority program "Ferroptosis: from Molecular Basics to Clinical applications" (SPP2306).

The work was also conducted as part of the DeciFerr (Deciphering and exploiting ferroptosis regulatory mechanism in cancer) project led by Professor Friedmann Angeli. Since May 2024, the project has received funding from the European Research Council (ERC) through an ERC Consolidator Grant worth nearly two million euros.