Investigation of Inhibition Effect of Some Chemotherapeutic Drugs on Human Serum Paraoxonase-1 (PON1)

We examined the effects of two different drugs (cladribine and mitoxantrone), which are frequently used in chemotherapeutic treatment, on human serum paraoxanase1 (PON1) enzyme activity in vitro. Chemotherapeutic drugs decreased in vitro PON1 activity. Cladribine and mitoxantrone inhibition mechanism were not competitive inhibitors. IC50 values for cladribine and mitoxantrone were calculated as 0.077 mM and 0.099 mM, respectively, and Ki constants were calculated as 0.057 ± 0.016 mM and 0.067 ± 0.027 mM, respectively. IC50 and Ki values showed that cladribine has a stronger inhibition. The results we found showed that these drugs, which are frequently used in chemotherapeutic treatment, inhibit enzyme activity with the same inhibition mechanisms at low doses.