Ultraviolet-treated riboflavin induces ROS-mediated apoptosis via inhibiting mitochondrial complex I in acute myeloid leukemia.

Acute myeloid leukemia (AML) remains challenging due to drug resistance and relapse, and novel therapeutic approaches are urgently needed. Here, we demonstrated that ultraviolet-treated riboflavin (RF-UV) elicited strong antileukemia effects in AML cell lines and primary patient samples, while showing minimal toxicity in normal cells. Mechanistically, inhibition of mitochondrial respiratory Complex I by RF-UV elevated reactive oxygen species (ROS) levels and resulted in ROS-mediated apoptosis, endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Crucially, in vivo research showed RF-UV considerably slowed the development of AML and extended the survival time of mice. Our research unveiled the clinical application potential of RF-UV as a complex I inhibitor in leukemia treatment.