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Öğe A Comparative Study on In vitro Anti-cancer and In vivo Anti-angiogenic Effects of TRPC Blockers Pyr-3 and SKF-96365(Bentham Science Publ Ltd, 2023) Kiyan, Hulya Tuba; Uvez, Ayca; Erkisa, Merve; Ikitimur-Armutak, Elif Ilkay; Yilmazer, Nadim; Esener, Osman Behzat Burak; Kutucu, Deniz ErolIntroduction Angiogenesis is involved in many physiological and pathological conditions including cancer. A number of TRP channels induce angiogenesis, promote cell proliferation or induce apoptosis in several types of human cancers. Therefore, TRP channels may be considered potential pharmacological targets for therapeutic options of disorders caused by insufficient angiogenesis or aberrant vascularization. Aims This study aimed to comparatively investigate in vitro anti-cancer and in vivo anti-angiogenic effects of TRPC blockers Pyr-3 and SKF-96365. Methods For anti-cancer effects, four cancer cell lines (MDA-MB-231, A549, PC-3, and HCT-116) were used. In vivo anti-angiogenic effects were investigated by employing in vivo CAM assay of fertilized hen eggs. Results Pyr-3 affected cell viability in a dose-dependent manner, all concentrations of SKF-96365 significantly reduced cell viability in all cell lines. Pyr-3 and SKF-96365 at concentrations of 2.5 & mu;g/pellet and 50 & mu;g/pellet, respectively inhibited in vivo angiogenesis significantly. Conclusion The concentration of 2.5 & mu;g/pellet caused no irritation, whereas 50 & mu;g/pellet produced some slight irritation. Apart from their anti-cancer effects, our findings indicate that Pyr-3 and SKF-96365 may be promising anti-angiogenic agents for the treatment of angiogenesis-related disorders.Öğe Donkey milk kefir induces apoptosis and suppresses proliferation of Ehrlich ascites carcinoma by decreasing iNOS in mice(Taylor & Francis Ltd, 2018) Esener, Osman Behzat Burak; Balkan, B. M.; Armutak, Elif İlkay İkitimur; Uvez, A.; Yıldız, Günay; Hafizoglu, M.; Gurel-Gürevin, E.; Yılmazer, NedimDonkey milk and donkey milk kefir exhibit antiproliferative, antimutagenic and antibacterial effects. We investigated the effects of donkey milk and donkey milk kefir on oxidative stress, apoptosis and proliferation in Ehrlich ascites carcinoma (EAC) in mice. Thirty-four adult male Swiss albino mice were divided into four groups as follows: group 1, administered 0.5ml water; group 2, administered 0.5ml water + EAC cells; group 3, administered 0.5ml donkey milk + EAC cells; group 4, administered 0.5ml donkey milk kefir + EAC cells. We introduced 2.5 x 10(6) EAC cells into each animal by subcutaneous injection. Tap water, donkey milk and donkey milk kefir were administered by gavage for 10days. Animals were sacrificed on day 11. After measuring the short and long diameters of the tumors, tissues were processed for histology. To determine oxidative stress, cell death and proliferation iNOS and eNOS, active caspase-3 and proliferating cell nuclear antigen were assessed using immunohistochemistry. A TUNEL assay also was used to detect apoptosis. Tumor volume decreased in the donkey milk kefir group compared to the control and donkey milk groups. Tumor volume increased in the donkey milk group compared to the control group. Proliferating cell nuclear antigen levels were higher in the donkey milk kefir group compared to the control and donkey milk groups. The number of apoptotic cells was less in the donkey milk group, compared to the control, whereas it was highest in the donkey milk kefir group. Donkey milk administration increased eNOS levels and decreased iNOS levels, compared to the control group. In the donkey milk kefir group, iNOS levels were significantly lower than those of the control and donkey milk groups, while eNOS levels were similar to the control group. Donkey milk kefir induced apoptosis, suppressed proliferation and decreased co-expression of iNOS and eNOS. Donkey milk promoted development of the tumors. Therefore, donkey milk kefir appears to be more beneficial for treating breast cancer than donkey milk.Öğe Protective effect of Spirulina platensis against cell damage and apoptosis in hepatic tissue caused by high fat diet(Taylor & Francis Inc, 2016) Yiğit, Funda; Gürel Gürevin, Ebru; İşbilen Başok, Banu; Esener, Osman Behzat Burak; Bilal, T.; Keser, O.; İkitimur Armutak, Elif; Yılmazer, N.Spirulina platensis is a microalga that may be a source of antioxidants that can reduce body fat deposition. Consumption of a high fat diet produces elevated blood lipid levels, inflammation and apoptosis. We investigated the possible effects of S. platensis on the blood lipid profile, and liver inflammation and apoptosis in rats fed a high fat diet. Sixty-four young male rats were divided into eight equal groups. The control group was fed a basic diet. The experimental groups were fed a diet for 60 days that was prepared by mixing variable amounts of 43% vegetable oil and 10% cholesterol with or without 3% S. platensis mixed with the basal diet. Blood and liver tissue samples were collected from each animal. Serum samples were used to analyze lipid parameters, total antioxidant status and total oxidant status. iNOS and eNOS were determined by immunohistochemistry. TUNEL staining was used to detect apoptosis to investigate a possible connection between inflammation and apoptosis in the liver tissue. The relations between fat deposition and liver degeneration were assessed by Sirius red staining and alpha-smooth muscle actin immunostaining. S. platensis reduced serum HDL-C, LDL-C and triglyceride, increased HDL-C levels in rats fed a high fat diet to near control levels, and reduced iNOS levels and increased eNOS levels in the liver tissue compared to vegetable oil and cholesterol treated groups. The apoptotic index was reduced in the groups that were fed a high fat or a basic diet when supplemented with S. platensis.Öğe Spirulina platensis affects factors involved in spermatogenesis and increases ghrelin receptors in testis tissue of rats fed a high-fat diet(Polska Akad Nauk, Polish Acad Sciences, Univ Warmia & Mazury Olsztyn, 2017) Esener, Osman Behzat Burak; Gurel-Gürevin, E.; Isbilen-Basok, B.; Yigit, F.; Bilal, T.; Altiner, A.; Armutak, Elif İlkay İkitimur; Yılmazer, NadimGhrelin is a peptide hormone which plays important role in maintaining growth hormone release and energy homeostasis in vertebrates. Spirulina platensis (SP) has antioxidant and hypolipidemic effects due to its ingredients. In this study we aimed to investigate the effects of SP on the testicular structure and relation between ghrelin and testosterone in the testis of rats fed a high fat diet (HFD). Sixty four young adult male rats were used and divided to 8 equal groups. Experimental groups received addition of 10% cholesterol (CHL), 43% hydrogenated vegetable oil (HVO) and 3% SP alone or in combination to basal diet while the control group received only basal diet. Serum ghrelin and testosterone levels were measured with ELISA. Receptors for ghrelin and androgen were detected with immunohistochemistry. For histomorphometric investigation, tubulus seminiferus, intertubular area, tubulus seminiferus lumen, Leydig cell nucleus, Sertoli cell nucleus, germ cell nucleus, spermatocyte nucleus and elongated spermatid volume densities were determined stereologically. Serum ghrelin level was increased especially in HVO and CHL combination group compared to the control while serum ghrelin levels were close to control levels in SP-received groups. Ghrelin receptor level was increased in tubulus seminiferus with HVO+CHL administration but this effect was, however, limited in HVO+CHL and SP challenged groups. HVO+CHL administration caused a significant decrease in Leydig cell nucleus volume density, as well as in all SP-received groups, compared to the control. Significantly increased spermatocyte nucleus volume density in cholesterol-receiving groups was decreased to control level with SP alone and its combinations.
