Browsing by Author "Hanoglu, A"

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    Cellular Behavior of Colchicum troodi Treated Primary and Metastatic Colon Adenocarcinoma Cell Lines
    Yavuz, DÖ; Becer, E; Vatansever, HS; Kabadayi, H; Hanoglu, A; Meriçli, F; Meriçli, AH
    Colchicum troodi belongs to Colchicaceae family that particularly rich in flavonoids, phenolic acids, tannin, fatty acids and alkaloids such as colchicine. The aim of this study was to investigate the anti-proliferative and protective effects of Colchicum troodi ethanolic extract toward relevant molecular signalling pathways on Colo-320 primer and Colo-741 metastatic colon adenocarcinoma cell lines. Colchicum troodi was collected and extracted. Different concentrations of Colchicum troodi extract were incubated for 24 h and 48 h with Colo-320 and Colo-741 cells. Cell growth and cytotoxicity were measured by MTT assays. Anticancer and antiprolifetarive activities of Colchicum troodi were investigated by immunocytochemistry using antibodies directed against to beta-catenin, LGRS, jagged 1, IHH, CD133 and Ki-67 in Colo-320 and Colo-741 cells. In the MTT assay, 10 mu g/ml and 5 mu g/ml Colchicum troodi extract were found to be active against Colo-741 and Colo-320 cells, respectively. Colchicum troodi extract significantly increased caspase beta-catenin immunoreactivities while IHH immunostaining intensity was decreased in Colo-741 cells. We conclude that Colchicum troodi extract increased beta-catenin via Wnt/beta-catenin pathway in Colo-741 cells. Interestingly, it decreased IHH immunoreactivities which is an antagonist of constitutive activity of Wnt/ beta-catenin signaling and is assumed to play protective act during carcinogenesis.
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    An Endemic Plant of Cyprus, Origanum majorana: Is It A New Alternative Natural Product for Malaria Treatment?
    Güler, E; Özbilgin, A; Becer, E; Hanoglu, A; Sanlidag, T
    Malaria still remains to be a public health threat and one of the most important infectious diseases to get attention from World Health Organization. No domestic malaria cases have been reported on the island of Cyprus since 1948, as a result of successful elimination process. All of the malaria cases detected in recent years are imported cases. As known, hundreds of medicines are obtained from plants and traditional medicine are used in endemic places of malaria. The cause of malaria - Plasmodium parasites, are developing resistance to antimalarial drugs. Hence, research on plant extracts and essential oils have gained great interest in recent years to obtain new and safe agents/substances. In our study, it was aimed to investigate the in vivo antimalarial activities of essential oils obtained from Origanum dubium, Origanum majorana, Salvia fruticosa and Laurus nobilis plants which grows in Northern Cyprus against Plasmodium berghei - the rodent malaria agent. Plants were collected in appropriate seasons and were dried to obtain and analyze essential oils via Clevenger Apparatus system. L929 mouse fibroblast cell line and MTT [3-(4.5-dimethylthiazole-2-yl) -2.5-diphenyltetrazolium bromide] kit were used to determine the cytotoxic activities of the essential oils obtained. In our study, total of 36 mice (Balb/c) of 6 groups (6 mice in each group) were formed: chloroquine group (CG) (50 mg/kg) as malaria reference group, untreated control group (UTCG), O. dubium (OD) (20 mg/kg), O.majorana (OM) (20 mg/kg), S.frutikosa (SF) (20 mg/kg) and L.nobilis (LN) (20 mg/kg). The essential oils were given to mice infected with P.berghei strain orally on 0, 1, 2 and 3rd days (4 times in total). Blood was taken from the tail end of each mouse 24 hours after the last treatment and blood collection was continued every two days until the mice died. Withdrawn blood taken from the mice were prepared as a thin smear and stained with Giemsa. Then, parasitemia percentages in each smear were calculated. As a result of the cytotoxicity tests, cytotoxic activity was not found at 100 mu g/ml (20 mg/kg) in all oils except OD essential oil. While the mice receiving chloroquine continued their lives with the disappearance of the parasite on the 6th day, the mice in the UTCG died on the 9th day. The parasitemia rate reached 35% in the OM group on the 23rd day, in the OD group on the 21st day and in the other groups (SF and LN) on the 14th day and the mice have died. In our study, the difference between the life span in all groups was found statistically significant (ps <= 0.001). As a result, the essential oils O.majorana (14 days increase according to UTCG) an endemic plant of Cyprus and O.dubium (12 days increase according to UTCG) which had an antimalarial effect, decreased parasitemia and increased the life span of mice more than two times, indicated that they could be a source for the acquisition of new antimalarial molecules.
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    The effect of Colchicum pusillum in human colon cancer cells via Wnt/β-catenin pathway
    Becer, E; Hanoglu, DY; Kabadayi, H; Hanoglu, A; Vatansever, S; Yavuz, DÖ; Meriçli, F; Meriçli, AH
    Objective: Colchicum pusillum belongs to the family Colchicaceae that particularly rich in tropolonic alkaloids. The aim of this study was to investigate the cytotoxicity and in vitro anticancer activity of Colchicum pusillum ethanolic extract on Colo-320 primer and Colo-741 metastatic colon adenocarcinoma cell lines. Materials and methods: Colchicum pusillum was collected and extracted with ethanol. Different concentrations of Colchicum pusillum extract were incubated for 24 h and 48 h with Colo-320 and Colo-741 cells. Cell growth and cytotoxicity were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Anticancer and antiproliferative activities of Colchicum pusillum were investigated by immunocytochemistry using antibodies directed against to beta-catenin, Ki-67, LGR-5 Ki-67, DKK1, Frizzled-4, Wnt4, Wnt7a and caspase3 in Colo-741 cells. Results: All concentrations of Colchicum pusillum extract had toxic effect in Colo-320 cells. Because of this, we used Colchicum pusillum extract at 20 mu g/ml for evaluate anticancer activities only in Colo-741 cells. As a result of immunohistochemical staining, beta-catenin, LGR-5 and caspase-3 immunoreactivities were significantly increased while Wnt7a immunostaining intensity was decreased in Colo-741 cells. Conclusion We conclude that Colchicum pusillum extract increased beta-catenin and LGR-5 via Wnt/beta-catenin pathway in colon cancer cells. Interestingly, it decreased other signaling molecule, Wnt7a which is assumed to play protective role during carcinogenesis. Also, it increased significantly caspase-3 immunoreactivity showing that apoptotic pathways were triggered.
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    Comparative phytochemical studies on the roots of Polygala azizsancarii and P. peshmenii and neuroprotective activities of the two xanthones
    Çalis, I; Becer, E; Ünlü, A; Aydin, ZU; Hanoglu, A; Vatansever, HS; Dönmez, AA
    Six known sucrose mono-, di- and triesters and five xanthone derivatives were isolated from the roots of Polygala peshmenii Eren, Parolly, Raus & Kurschner which is a narrow species endemic to Turkiye. Among the xanthones, 1,7-dihydroxy-2,3-methylenedioxy-5,6-dimethoxy-xanthone is an undescribed compound isolated for the first time from a natural source. The studies on the roots of P. azizsancarii Do & BULL;nmez have resulted in the isolation of four known compounds including sucrose mono-, di- and triesters. The structures of the sucrose esters and xanthones isolated from P. azizsancarii and P. peshmenii were established by spectroscopic methods, including 1DNMR (1H NMR, 13C NMR, DEPT-135), 2D-NMR (COSY, NOESY, HSQC, HMBC). Neuroprotective activities of two xanthones, 1,3,6-trihydroxy-2,5,7-trimethoxyxanthone and 3-O-& beta;-D-glucopyranosyloxy-1,6-dihydroxy-2,5,7-trimethoxyxanthone isolated from the roots of P. azizsancarii were evaluated in vitro using in a cellular model of Alzheimer's disease. SKNAS human neuroblastoma cells were used in the study and treated with different consecrations of A & beta;25-35 oligomer for up to 48 h. Cell viability was evaluated using MTT assay. The distribution of & beta;-amyloid, & alpha;-synuclein, tau, JAK2, STAT3, caspase 3 and BMP-2 were investigated using indirect immunoperoxidase staining. Our results suggested that both xanthones control tau aggregation with no effect on & beta;-amyloid plaque formation. In addition, for neuronal pathophysiology in AD cell model, decreased distributions of JAK/ STAT3 and BMP2 signaling pathways were demonstrated, therefore they play a role in the protective effect on neurons in neurodegenerative disease. A significant decrease in caspase 3 immunoreactivity was detected after the administration of both compounds in AD cells. Therefore, both compounds control neuronal pathophysiology and rescue cell death in AD disease.
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    The Effect of Cynara cornigera L. in HepG2 Hepatocellular Carcinoma Cells
    Sanlidag, E; Becer, E; Çalis, I; Baser, KHC; Hanoglu, A; Göger, F; Vatansever, HS
    Amongst all cancer types, liver cancer is the fourth leading cause of cancer mortality. It is frequently stated as hepatocellular carcinoma (HCC) and occurs in hepatocytes. Genetic alterations of hepatocytes such as Wnt/beta-catenin and JAK / STAT signaling pathways play a key role for the development of the HCC. Currently, there are a few available treatments for HCC; such treatments include transplantation, surgical resections and anticancer drugs. Most of the anti-cancer drugs target the signaling pathways for achieving an effective treatment. However, these treatments have some undesirable side effects. Thus, there is a need for discovering alternative anti-cancer agents with no or lesser side effects. Plant constituents are promising anti-cancer agents. Cynara cornigera L. contains plenty of phenolic compounds including quercetin, apigenin, etc. This study aimed to analyze the anti- cancer property of the fractionated methanol extract of the flowers of C. cornigera. All the fractions obtained were analyzed to determine the cytotoxic activity on HepG2 cells. Two of the fractions containing polyphenolic compounds had a significant cytotoxic activity related to non-canonical Wnt11 signaling pathways on HepG2 cells.
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    The cytotoxic and antiproliferative effect of Polygala saponin XLIV on the human colorectal carcinoma cell line
    Becer, E; Hanoglu, A; Ünlü, A; Aydin, ZU; Dönmez, AA; Jurt, S; Vatansever, SH; Çalis, I
    Objectives Saponins are secondary metabolites naturally found in plants with diverse pharmacological properties such as anticancer. This research aimed to explore the anti-cancer properties of Polygalasaponin XLIV (PS-XLIV) in a human colorectal carcinoma cell line derived from Polygala vulgaris roots.Methods HCT166 cells were treated with different PS-XLIV concentrations and incubated for 24 and 48 h. We used immunocytochemistry to investigate PS-XLIV's anti-cancer properties, employing antibodies targeting WNT3A, WNT11, STAT3, beta-catenin, and Ki-67. The IC50 value of PS-XLIV was 80 mu g/mL in HCT116 cells. WNT11, STAT3, beta-catenin, and Ki-67. Immunoreactivities significantly decreased in PS-XLIV-treated HCT116 cells than in control group cells.Results After PS-XLIV treatment, the epithelial morphology of cells was protected; however, the number of cells was less than that of the control group cells. While WNT3A immunoreactivity was similar in both groups, WNT11 and beta-catenin immunoreactivities were decreased after PS-XLIV application. In addition, the PS-XLIV treated group exhibited significantly weaker Ki-67 immunoreactivity, STAT3 immunoreactivty was moderated after PS-XLIV application.Conclusions For the first time, the anticancer effects of PS-XLIV isolated from P. vulgaris on HCT116 cells were shown. The anticancer effect may involve PS-XLIV reducing WNT11, beta-catenin, STAT3, and Ki-67 activation pathways in HCT116 cells.