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

详细信息    查看全文

• 作者：Zuhal Alim and Şü ; krü ; Beydemir
• 刊名：Chemical Biology & Drug Design
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：88
• 期：2
• 页码：188-196
• 全文大小：836K
• ISSN：1747-0285

文摘

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. K_i 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.