Study published in PNAS also showed how tolrestat inhibits AKR1B10’s ability to decrease vitamin A levels.
Researchers say that they have created a 3-D structure of AKR1B10, an enzyme that appears when precancerous lesions show up and is detected in large quantities only in lung cancers, particularly those caused by smoking.
According to the investigators, experiments using test tubes and cell cultures revealed that the enzyme lowers the levels of the most active form of vitamin A, retinoic acid, also an anticancerous agent. This is achieved by its retinal reductase activity, which favors chemical reduction transformation, thus causing retinal, the precursor of retinoic acid, to transform into its least active form, retinol.
To understand why the enzyme acts this way, the team obtained and studied its 3-D structure and located the elements responsible for its role in the onset of cancer among smokers.
Researchers were also able to observe how the substance tolrestat, used as an inhibitor of the enzyme AKR1B1 (aldose reductase), responsible for many secondary complications of diabetes, also worked to inhibit the activity of the enzyme AKR1B10.
Scientists at the Universitat Autònoma de Barcelona led the study, which also included collaborators from the Biomedical Research Institute of the Science Park of Barcelona, the Institute of Molecular Biology of Barcelona, the Catalan Institute for Research and Advanced Studies, and the University of Vigo. The study will be published in the online edition of Proceedings of the National Academy of Science.
