Some Anticancer Agents Act on Human Serum Paraoxonase-1 to Reduce Its Activity


Alim Z., BEYDEMİR Ş.

Chemical Biology and Drug Design, vol.88, no.2, pp.188-196, 2016 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 88 Issue: 2
  • Publication Date: 2016
  • Doi Number: 10.1111/cbdd.12746
  • Journal Name: Chemical Biology and Drug Design
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.188-196
  • Keywords: anticancer agents, enzyme–drug interaction, high-density lipoprotein, inhibition, paraoxonase
  • Bilecik Şeyh Edebali University Affiliated: Yes

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.