On Friday, May 12th, Dr. Milica Vukotić, a researcher from the Molecular Oncology Group, held a Scientific Seminar at the Institute for Medical Research titled: “Old therapeutic, new molecular mechanisms: Hydroxyurea activates nitric oxide synthase in erythroid progenitors.”
During the Seminar, she presented findings suggesting that hydroxyurea, a drug used for decades in the treatment of hematological malignancies, may exert its effects through a previously unknown mechanism: direct stimulation of the NOS2 enzyme. This effect was demonstrated through in vitro enzymatic assays and supported by molecular modeling.
“In a reaction tube containing recombinant NOS2, substrate, cofactors, and increasing concentrations of hydroxyurea, we were able to detect a rise in nitrite and citrulline levels, clearly indicating enhanced enzymatic activity,” said Dr. Vukotić during her presentation.
These results highlight the potential to further improve the efficacy of hydroxyurea treatment in myeloproliferative neoplasms and chronic myeloid leukemia, especially when combined with L-arginine or other available chemical stimulators of NOS2 and NOS3.
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