title: Some Anticancer Agents Act on Human Serum Paraoxonase-1 to Reduce Its Activity.
abstract: Human serum paraoxonase (hPON1) is an important antioxidant enzyme. It protects low-density lipoproteins against oxidative stress and prevents atherosclerosis development. Anticancer agents have cardiotoxic effects, and this situation can lead to significant complications. Our aim was to evaluate the in vitro effects of some of the anticancer agents such as cetuximab, paclitaxel, etoposide, docetaxel, and ifosfamide on the activity of hPON1 in this study. For this reason, PON1 was purified from human serum with a specific activity of 3654.2 EU/mg and 16.84% yield using simple chromatographic methods. The five chemotherapeutic agents dose dependently decreased in vitro hPON1 activity. IC50 values for cetuximab, paclitaxel, etoposide, docetaxel, and ifosfamide were 0.0111, 0.042, 0.226, 0.665, and 23.3 mm, respectively. Ki constants were 0.0194, 0.0165, 0.131, 0.291, and 8.973 mm, respectively. The inhibition mechanisms of cetuximab, etoposide, docetaxel, and ifosfamide were non-competitive, and for paclitaxel was competitive. Consequently, inhibition of hPON1 by these anticancer agents may explain some of the cardiotoxic actions of these drugs.
authors.affiliation: Biochemistry Division, Department of Chemistry, Faculty of Science and Arts, Ahi Evran University, Kırşehir, 40000, Turkey.
authors.forename: Zuhal
authors.initials: Z
authors.lastname: Alim
authors.affiliation: Biochemistry Division, Department of Chemistry, Faculty of Sciences, Atatürk University, Erzurum, 25240, Turkey.|Department of Food Sciences, Faculty of Engineering, Iğdır University, Iğdır, Turkey.
authors.forename: Şükrü
authors.initials: Ş
authors.lastname: Beydemir
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D043303:Aryldialkylphosphatase / Q000097:blood* / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D043303:Aryldialkylphosphatase
keywords: anticancer agents; enzyme-drug interaction; high-density lipoprotein; inhibition; paraoxonase