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    Combination of 2 Bioactive Compounds for Treatment of Breast Cancer: Triterpenoid Cucurbitacin I and Phenolic CAPE
    (Sage Publications Inc, 2019) Karakus, Fuat; Yilmaz, Kadir; Eyol, Ergul; Unuvar, Songul
    It has been demonstrated that both cucurbitacin I (Cu I) and caffeic acid phenethyl ester (CAPE) have anticancer activities. The current study aimed to examine the proliferation, migration, and colony formation actions of Cu I and CAPE on MCF-7 and MDA-MB-231 human breast cancer cells. The antimigration, antiproliferative, and colony inhibition effects of different dosages of Cu I, CAPE, and Cu I + CAPE on cells were determined by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) cell viability assay, wound healing, and colony formation assays, respectively. Compared with single treatment, combination of 2 bioactive compounds enhanced the anticancer activity. When Cu I and CAPE were combined, a strong inhibitor effect was shown on cell growth, colony formation, and cell migration compared with the compounds used singly. The concomitant treatment with Cu I and CAPE showed stronger antiproliferative activities on both MCF-7 and MDA-MB-231 cells compared with individual treatment with either Cu I or CAPE. Caffeic acid phenethyl ester is a specific inhibitor of Nuclear factor-kappa B (NF-kappa B). It shows anticancer activity depending on this inhibition. It is a bioactive phenolic compound that is derived from propolis. Cucurbitacin I is a selective Januskinase/signal transducer and a transcription-3 signal pathway inhibitor. Combination of these 2 natural anticancer compounds is beneficial in the treatment of cancer, as well as the side effects associated with classical chemotherapeutics not being observed with the use of these compounds.
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    Cytotoxic Effects of Cucurbitacin I and Ecballium elaterium on Breast Cancer Cells
    (Natural Products Inc, 2018) Yilmaz, Kadir; Karakus, Fuat; Eyol, Ergul; Tosun, Emir; Yilmaz, Ismet; Unuvar, Songul
    The objective of this study was to investigate the inhibitory effect of cucurbitacin I (CuI) and Ecballium elaterium L. (fruit juice and chloroform extract) on breast cancer cells (MCF-7 and MDA-MB-231). The Cul content of E. elaterium fruit juice and chloroform extract was quantified using high performance liquid chromatography. The cytotoxic effects of the fruit juice, chloroform extract and CuI were determined by MTT, wound healing and colony formation assays; all had an anti-proliferative activity on the breast cancer cells. Clarifying the mechanisms of cucurbitacins will enable the identification of new molecular targets for breast cancer therapy.
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    Growth inhitory effects of Cucurbitacin I on breast cancer cells
    (Lippincott Williams & Wilkins, 2015) Yilmaz, Kadir; Karakus, Fuat; Tosun, Emir; Eyol, Ergul
    [Abstract Not Available]
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    In vitro effect of carbonic anhydrase inhibitor acetazolamide on cell viability, migration and colony formation of colorectal cancer cells
    (Springer, 2018) Karakus, Fuat; Eyol, Ergul; Yilmaz, Kadir; Unuvar, Songul
    Acidification of extracellular medium in malignant tumors increases the invasive behaviors of cancer cells. In normal healthy tissues, acid production is catalyzed by carbonic anhydrases. Some of the carbonic anhydrase enzymes are overexpressed in certain types of cancer. The present study aimed to investigate the effect of acetazolamide, a potent carbonic anhydrase inhibitor, on in vitro cultivated cancer cells. Three different assays (MTT test, wound healing and clonogenic assay) were performed using human colorectal adenocarcinoma cells (SW620) to evaluate the suppressive effect of acetazolamide, on the colorectal cancer cells migration ability, colony formation and cell viability. The dose-dependent (1-1000 mu M) reducing effect of acetazolamide on the cell viability was more significant within the first 48 h. This inhibitory effect of acetazolamide was found to be decreased at 72 h, and affects cells migration ability of cells at 24 and 48 h. Acetazolamide was observed to inhibit the cell viability, migration and colony formation ability of cells, depending on dose.
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    Inhibition of cell proliferation, migration and colony formation of LS174T Cells by carbonic anhydrase inhibitor
    (Makerere Univ, Fac Med, 2018) Karakus, Fuat; Eyol, Ergul; Yilmaz, Kadir; Unuvar, Songul
    Background: Metastasis is the leading cause of cancer deaths. Migration of tumor cells is an important stage in metastasis. Therefore, recent studies have focused on clarifying migration and migration-dependent cell functions such as angiogenesis, wound healing, and invasion. Objectives: In the present study, we aimed to investigate the effect of acetazolamide, which is a classical carbonic anhydrase inhibitor, on the cell viability, migration, and colony forming capacity of human LS174T colorectal cancer cells. Methods: Three different cell culture techniques (MTT test, wound healing and clonogenic assay) were performed in this in vitro study on colorectal cancer cells. Results: Acetazolamide reduced the cell viability, migration and colony formation ability of cells depending on dose. There was no significant difference between the cells treated with acetazolamide with 1 mu M dose and the control. However, it can be concluded that acetazolamide exerts its effect on human colorectal cancer cells at 10-1000 mu M concentrations. Conclusion: Acetazolamide was observed to significantly inhibit the cell viability, colony forming capacity, and migration ability in the culture medium of LS174T cells. This inhibitor effect of acetazolamide was observed to be dependent on the concentration in medium.
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    The relationship between neopterin and hepatitis B surface antigen positivity
    (De Gruyter Poland Sp Z O O, 2018) Unuvar, Songul; Aslanhan, Hamza; Tanriverdi, Zubeyde; Karakus, Fuat
    Hepatitis B is a life-threatening viral liver infection caused by the hepatitis B virus. Neopterin is regarded as an immunologic biomarker of several diseases related to activation of the cellular immune system. Hepatitis B infection is associated with increased production of cellular immune system markers. We aimed to investigate whether there is a relationship between hepatitis B surface antigen-positivity (HBsAg +) and neopterin to determine the role of neopterin in the early diagnosis of hepatitis B infections. Seventy-two HBsAg (+) patients with normal liver function tests and forty-three controls were included in the study. Neopterin levels were 17.6 +/- 0.13 nmol/L in HBsAg (+) patients; and 9.12 +/- 0.09 nmol/L in infection-free controls, respectively. Compared to the control group, a statistically significant increase (p < 0.001) in the serum neopterin levels of the patients was observed. No significant relationship was determined between neopterin levels and age/sex (both, p > 0.05). With overstimulation of interferon-gamma, the production of neopterin increases by monocytes/macrophages. Likewise with other diseases associated with an activated cellular immune system, this study shows that neopterin can be a predictive biomarker for persistent carriers of hepatitis B infection.
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    Screening and toxicity evaluation of natural compounds as adenosine 2a and 2b receptor ligands: insights from molecular docking, dynamics, and ADMET analysis
    (Taylor & Francis Ltd, 2025) Karakus, Fuat; Alagoz, Mehmet Abdullah; Kuzu, Burak
    Recent studies suggest that immunological and inflammatory responses in cardiovascular disorders, such as hypertension, myocardial infarction, ischemia injury, heart failure, arrhythmias, and atherosclerosis, may be affected by changes in the adenosine system. Pharmacological modulation of adenosine occurs through its receptor subtypes. In numerous preclinical studies, the activation of adenosine receptor 2A (A2AR) or the blockade of adenosine receptor 2B (A2BR) has shown promising results against cardiovascular diseases. This in silico study aimed to identify potential natural compounds that can activate A2AR or block A2BR without causing toxicity. Natural compounds were screened using COlleCtion of Open Natural ProdUcTs (COCONUT) or Natural Product Activity and Species Source Database (NPASS) databases to find agonists for A2AR or an antagonists/inverse agonists for A2BR. These compounds were then pre-filtered based on their toxicity profiles. The remaining compounds were subjected to molecular docking against A2AR and A2BR followed by molecular dynamics simulations were conducted. Finally, selected compounds' ADMET properties were determined using ADMETlab 2.0 web tool. Ultimately, one novel natural compound with potential agonistic activity (COCONUT IDs: CNP0450901) for A2AR and one antagonist/inverse agonist (rauwolscine) for A2BR were identified.