Browsing by Author "Sadi, Gokhan"

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Evaluation of the Biological Activities of Olivetoric Acid, a Lichen-Derived Molecule, in Human Hepatocellular Carcinoma Cells
(Springer-verlag Italia Srl, 2021) Emsen, Bugrahan; Sadi, Gokhan; Bostanci, Aykut; Gursoy, Nuray; Emsen, Ayca; Aslan, Ali
Many lichen secondary metabolites contributed to the field of pharmacology as an active ingredient of different drugs for years. In the present study, we aimed to test the anticancer activity of olivetoric acid (OA), which we isolated from Pseudevernia furfuracea (L.) Zopf in human hepatocellular carcinoma cells (HepG2). In addition, we used non-tumoral human liver cells (THLE2) to test the level of side effects of OA in vitro. For this purpose, cytotoxic (apoptotic and necrotic), oxidant, genotoxic activities and expression levels of apoptotic genes caused by different concentrations (12.5-400 mg/L) of OA were tested on both cells. Flow cytometric and cytotoxicity tests (MTT and LDH) revealed that OA (100-400 mg/L) had a higher rate of apoptotic effects on HepG2 cells compared to THLE2. Total oxidative stress and oxidative DNA damage levels caused by all concentrations of OA on HepG2 cells was significantly (p < 0.05) higher compared to negative control. Trials with concentrations of 100-400 mg/L significantly (p < 0.05) increased total antioxidant capacity on THLE2 cells compared to the control group. As a result, based on human hepatocellular carcinoma, it is hoped that OA may contribute to the combined or alternative treatment process.
In Vitro Evaluation of Cytotoxic, Oxidative, Genotoxic, and Apoptotic Activities of Physodic Acid From Pseudevernia Furfuracea in Hepg2 and Thle2 Cells
(Taylor & Francis Ltd, 2021) Emsen, Bugrahan; Sadi, Gokhan; Bostanci, Aykut; Aslan, Ali
In the present study, cytotoxic (apoptotic and necrotic), antioxidant, prooxidant, genotoxic, and apoptosis-related genes expression modulatory effects of physodic acid (PA) isolated from Pseudevernia furfuracea on cancerous (HepG2) and healthy (THLE2) human liver cells were evaluated. Cytotoxic effects PA obtained from P. furfuracea on HepG2 and THLE2 cells were tested via MTT and LDH analyses. In order to determine genotoxic effect of PA, 8-OH-dG levels in the cells were measured. In addition, apoptotic or necrotic effects of PA on the hepatic cells were determined by qRT-PCR analysis. Cytotoxicity analyses revealed the cytotoxic effect of PA on HepG2 cells, which is much higher than THLE2 cells. Gene expression studies demonstrated the apoptotic effects of PA on HepG2 cells through both extrinsic and intrinsic pathways. PA increased the antioxidant capacity of THLE2 cells with increasing concentrations, which describes its antioxidant power. Additionally, none of the tested levels of PA caused oxidative DNA damage on THLE2 cells, but its high concentration increased genetic damages on HepG2. Taken together, P. furfuracea lichen and its metabolite, PA, would be a promising alternative for complementary treatments against liver cancer.
Modulation of Mrna Expression and Activities of Xenobiotic Metabolizing Enzymes, Cyp1a1, Cyp1a2, Cyp2e1, Gpx and Gstp1 by the Salicornia Freitagii Extract in Ht-29 Human Colon Cancer Cells
(inst Bioloska Istrazivanja Sinisa Stankovic, 2017) Altay, Ahmet; Kartal, Deniz Irtem; Sadi, Gokhan; Guray, Tulin; Yaprak, Ahmet Emre
Phase I-II detoxification and antioxidant enzymes are responsible for the detoxification and elimination of activated carcinogens, acting as important biomarkers for chemoprevention. Among them, cytochrome P450s plays a prominent role in the metabolic activation of xenobiotics. The herb Salicornia freitagii (SF) (Amaranthaceae) is known for its anticancer, antioxidant, antidiabetic and antiinflammatory activities. In this study, we determined the bioactive phenolics in the SF methanol extract and investigated its antiproliferative potential in HT-29 human colon cancer cells. We also investigated the modulation of some phase I and II enzyme (CYP 1A1, 1A2, 2E1, GSTP1 and GPx) mRNA expression and enzymatic activities by the SF extract and its major bioactive phenolic compounds. LC/MS-MS analysis showed that the main phenolic compounds of the methanolic SF extract are vanillic acid (48 mu g/100g) and p-coumaric acid (10.8 mu g/100g). SF extract, vanillic acid and p-coumaric acid exhibited high antiproliferative activities in HT-29 cells, with IC50 values of 81.79 mu g/mL, 98.8 mu M and 221.6 mu M, respectively. The mRNA expression levels of CYP1A2 and CYP2E1 were decreased, while those of GSTP1 and GPx in HT-29 cells were increased after application of either the SF extract or vanillic acid. The SF extract by itself also increased the activities of GPx and GSTP1 enzymes 1.68- and 1.49-fold, respectively. Our data indicate that the SF extract and its major bioactive compound, vanillic acid, could exert a modulatory effect on the expression of enzymes that are involved in xenobiotic activation and detoxification pathways in the gastrointestinal tract. For this reason, SF can be considered as a natural source of chemopreventive agents.