Investigation of the effect of Rosmarinus officinalis plant extract on PON 1 and CA-IX enzyme activities in hepatocellular carcinoma cell line

ABSTRACT Investigation of the Effect of Rosmari̇nus Offi̇cinali̇s Plant Extract on PON 1 and CA-IX Enzyme Activities in Hepatocellular Carcinoma Cell Line Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The carbonic anhydrase enzyme family (CA; EC 4.2.1.1) are zinc (Zn+2)-dependent metalloenzymes that catalyze the hydration of carbon dioxide (CO2) to produce bicarbonate (HCO3-) and hydrogen ions (H+). CA-IX is a cell surface glycoprotein of the CA family that increases the pH of the tumor microenvironment. In studies, it has been reported that CA-IX expression is high in hepatocellular carcinoma cells in a hypoxic environment and is associated with metastasis. Paraoxonase (PON; EC 3.1.8.1) enzyme is a calcium-dependent hydrolytic serum metalloenzyme that hydrolyzes paraoxon and eliminates its harmful effects. The PON family of enzymes regulates low oxidative stress, inflammation, and cell death in cancer patients. Paraoxonase 1 (PON1) is a PON family cell surface glycoprotein that regulates the redox system in tumor cells. It is known that the expression of PON-1 is decreased in hepatocellular carcinoma and is associated with inflammation and oxidative stress. In our study, the cytotoxic effects of phenolic compounds and various extracts obtained from Rosmarinus officinalis (Rosemary) species belonging to the Lamiaceae family will be examined by applying different concentrations of R. Officinalis plant extract in hepatocellular carcinoma cell line (HepG2). By investigating the relationship between PON1 enzyme and tumor-related CA-IX enzyme of R. Officinalis plant extract, it was aimed to show the effect of Rosmarinus officinalis, which is known as rosemary plant in the medical and pharmaceutical field with anti-inflammation, anti-cancer and antioxidant effects, on the enzyme levels of HepG2. In our study, R.Officinalis methanol and ethanol plant extracts showed antiproliferative effect on HCC cells at the level of CA-IX and PON1 enzymes.