Inhibitory Effect of Methotrexate (MTX) Used in Human Cancer Treatment on Paraoxonase-1 (PON1)

Background and Objective: Paraoxonase-1 (PON1) is a lactonase that plays a role in the destruction of carcinogenic free radicals and in reducing oxidative stress. In this article, it was aimed to investigate the inhibitory effect of methotrexate (MTX) on PON1. Materials and Methods: In this study, the inhibition between methotrexate used in cancer chemotherapy and PON1 was studied. Results: Methotrexate showed very strong inhibitory properties for human serum PON1, with an IC(50)value of 38.50 mu M and a mean K-i value of 42.36 mu M. Hence methotrexate showed competitive inhibition. Conclusion: The widespread use of methotrexate, a dihydrofolate reductase (DHFR) inhibitor, in the treatment of human cancers can be very harmful.

Automated summary

This study investigated the inhibitory effect of methotrexate on PON1, and the results showed that methotrexate competitively inhibited PON1, which could be harmful in the treatment of human cancers.