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

Hakan Söyüt, Yakup Ulutaş and Ekrem Köksal

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 IC₅₀ value of 38.50 μM and a mean K_i value of 42.36 μM. 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.

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