Researchers at the Rudolf Virchow Centre at the University of Würzburg announced on Mar. 13 that a lack of vitamin B2, also known as riboflavin, makes tumor cells more susceptible to a unique form of cell death called ferroptosis.
This finding is significant because it highlights how vitamin B2 metabolism not only protects healthy cells from oxidative damage but also helps cancer cells evade destruction. The study, published in Nature Cell Biology, suggests that targeting riboflavin-derived cofactors could weaken cancer cells' resistance to ferroptosis and make tumors more vulnerable.
The research group, led by Professor José Pedro Friedmann Angeli, focused on the protein FSP1, which supports cellular defense against cell death. Their experiments using genome editing and cancer cell models showed that when vitamin B2 was deficient, cancer cells became more sensitive to ferroptosis. "However, an inhibitor that can do this is still missing," said researcher Skafar. To address this gap, the team tested roseoflavin—a natural compound similar to vitamin B2 produced by bacteria—and found it could trigger ferroptosis in low concentrations. "It turned out that roseoflavin triggers ferroptosis in low concentrations," said Friedmann Angeli. "Our experiments show the feasibility of this concept." The results pave the way for developing targeted therapies based on inducing ferroptosis in cancer cells.
The next phase for the research group will be to develop inhibitors of vitamin B2 metabolism and evaluate their effectiveness in preclinical cancer models.
Friedmann Angeli said: "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." He added that understanding how vitamin B2 metabolism influences ferroptosis may have broader implications for other diseases where excessive or insufficient ferroptosis plays a role.
The study received funding from the German Research Foundation's priority programme on ferroptosis and from the European Research Council through an ERC Consolidator Grant awarded since May 2024.
