Scientists in Germany have uncovered how vitamin B2 helps cancer cells evade a powerful form of cell death. Their work opens a path toward new drugs that could strip tumors of this protection.
Vitamin B2 is best known as a nutrient we need to stay healthy. But new research suggests that, inside tumors, it may also be helping cancer cells stay alive.
A team from the Rudolf Virchow Centre at Julius-Maximilians-Universität Würzburg has discovered that riboflavin, or vitamin B2, supports a key survival system that shields cancer cells from a type of cell death called ferroptosis. By disrupting this vitamin pathway in the lab, the researchers were able to make cancer cells more vulnerable, pointing to a potential new strategy for cancer treatment.
“Vitamin B2 plays a crucial role in protecting cancer cells from ferroptosis, a special form of programmed cell death,” Vera Skafar, a doctoral student and member of a research group led by José Pedro Friedmann Angeli, a professor of translational cell biology, said in a news release.
The study, published in Nature Cell Biology, focuses on ferroptosis, a relatively recently described form of programmed cell death. Unlike better-known pathways such as apoptosis, ferroptosis is driven by iron and the buildup of damaging lipid peroxides — unstable molecules that attack cell membranes.
Under normal conditions, cells rely on antioxidant systems to keep this damage in check. Cancer cells, which often face high levels of stress, can ramp up these defenses to avoid ferroptosis and continue growing.
The Würzburg team zeroed in on riboflavin because the body cannot make it on its own; it must be obtained from foods such as dairy products, eggs, meat and green vegetables. Once absorbed, vitamin B2 is converted into cofactors that support many metabolic reactions, including those that protect cells from oxidative damage.
One of the proteins involved in this protection is FSP1, a major focus of Friedmann Angeli’s group. FSP1 helps defend cells against ferroptosis, and vitamin B2 helps FSP1 do its job.
Using genome editing tools and cancer cell models, the researchers reduced the availability of vitamin B2 and watched what happened. When the vitamin was lacking, cancer cells lost some of their ability to fend off oxidative damage and became more susceptible to ferroptosis.
That vulnerability is exactly what cancer therapies aim to exploit: pushing cancer cells over the edge while sparing healthy tissue as much as possible.
In theory, if scientists could selectively block vitamin B2 metabolism in tumors, they might be able to strip cancer cells of this protective shield and trigger their death through ferroptosis. But there is a major obstacle.
“However, an inhibitor that can do this is still missing,” Skafar added.
To explore what such an approach might look like, the team turned to roseoflavin, a natural compound produced by bacteria that closely resembles vitamin B2 in structure. Because of this similarity, roseoflavin can interfere with riboflavin-dependent processes.
In cancer cell models in the lab, the researchers tested roseoflavin as a stand-in for a future drug that might target vitamin B2 metabolism more precisely.
“It turned out that roseoflavin triggers ferroptosis in low concentrations,” Friedmann Angeli said in the news release. He added “our experiments show the feasibility of this concept.”
In other words, by disrupting riboflavin-related pathways, the team could push cancer cells toward ferroptosis, supporting the idea that vitamin B2 metabolism is a promising target for drug development.
The next phase of the work will be to move beyond roseoflavin and design more specific inhibitors of vitamin B2 metabolism. The Würzburg group plans to develop and test such compounds in preclinical cancer models to see whether they can safely and effectively weaken tumors’ defenses.
The implications may extend well beyond oncology. Ferroptosis has been linked to a range of conditions in which cell death is either excessive or poorly controlled.
“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,” Friedmann Angeli added.
That means understanding how vitamin B2 metabolism shapes ferroptosis could eventually inform treatments for brain disorders, transplant complications and injuries caused when blood flow is cut off and then restored, such as in heart attacks or strokes.
The project is part of a broader push to translate basic discoveries about ferroptosis into clinical advances.
For students and early-career scientists, the work is a reminder that even familiar nutrients can have surprising roles in disease. A vitamin that helps keep our cells healthy can, in the wrong context, also help cancer cells survive.
By mapping out these hidden connections, researchers hope to design therapies that turn a tumor’s strengths into weaknesses — and use the same molecular pathways that once protected it to bring about its destruction.