When vitamin B2 is deficient, tumor cells are susceptible to specific cell death. This was discovered by researchers at the Rudolf Virchow Center at the University of Wurzburg.
The human body cannot produce vitamin B2 itself, also known as riboflavin. You need to absorb important substances through your diet. This vitamin is found in dairy products, eggs, meat, and green vegetables. Metabolism converts it into molecules that protect cells from damage such as oxidation.
Researchers at the Rudolf Virchow Center (RVZ) at Julius-Maximilians-Universität Würzburg (JMU) have discovered that this function of the vitamin also has a downside. It also protects cancer cells.
Vitamin B2 plays an important role in protecting cancer cells from ferroptosis, a special form of programmed cell death. ”
Bella Scafar, PhD student
She is a member of a research group led by José Pedro Friedman Angeli, professor of translational cell biology. The results were published in a famous magazine natural cell biology.
Relationship between vitamin B2 and ferroptosis
The human body uses programmed cell death mechanisms to “kill” damaged or dangerous cells in a controlled manner without causing inflammation in surrounding tissue. In particular, ferroptosis is associated with many pathological conditions, including cancer and neurodegeneration.
Unlike other cell death pathways, ferroptosis is triggered when iron-induced lipid peroxidation overwhelms the cell’s antioxidant protection. Cancer cells often avoid ferroptosis by enhancing their redox defense systems. This study highlights that vitamin B2 metabolism is an important contributor to these defenses and suggests that targeting riboflavin-derived cofactors may weaken ferroptosis resistance and make tumors more vulnerable.
Potential inhibitor
The protein FSP1, the focus of the working group’s research, is one of the components responsible for protecting healthy cells from cell death. Vitamin B2 supports proteins in this role. Using genome editing and cancer cell models, researchers observed that vitamin deficiency made cancer cells more susceptible to ferroptosis.
Ideally, this could be used therapeutically. In other words, it should be possible to specifically trigger the death of cancer cells by turning off the vitamin B2 metabolic pathway. “However, we have not yet found an inhibitor that allows this,” Scafar says. The researchers addressed this limitation by utilizing roseoflavin, a natural compound produced by bacteria that has a vitamin B2-like structure.
Advancing the path to targeted cancer therapy using ferroptosis
In the lab, Professor Friedman Angeli’s team tested the active substance in cancer cell models. “We found that roseoflavin causes ferroptosis at low concentrations. Our experiments demonstrate the feasibility of this concept,” says the group leader. This study therefore paves the way for the development of targeted cancer treatments based on ferroptosis.
In the next step, the RVZ working group will focus on developing inhibitors of vitamin B2 metabolism. The aim is to evaluate its use in preclinical cancer models.
Dr. Friedman-Angeli added, “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 influences ferroptosis may have broader implications for diseases involving excessive or insufficient ferroptosis.
funding
This study was funded by the German Research Foundation (DFG) priority program “Ferrotosis: from molecular basics to clinical applications” (SPP2306). This was also carried out under the DeciFerr (Decoding and Exploitation of Ferroptosis Control Mechanisms in Cancer) project led by Professor Friedman Angeli. This has been funded by the European Research Council (ERC) with an ERC Consolidator Grant and almost €2 million from May 2024.
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Reference magazines:
Scafar, V. Others. (2026). Riboflavin metabolism forms FSP1-mediated ferroptosis resistance. natural cell biology. DOI: 10.1038/s41556-025-01856-x. https://www.nature.com/articles/s41556-025-01856-x
