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Abdurrahim Kocyigit Eray Metin Guler Ezgi Durmus Vildan Betul Yenigun Ebru Kanimdan Zeynep Ozman Oznur Yasar Ahmet Ceyhan Goren Emine Rumeysa Hekimoglu Hasan Huseyin Oruc Gokhan Aydogdu 《化学与生物多样性》2023,20(9):e202300591
In this study, we investigated the combined treatment of 5-fluorouracil (5-FU) and Anatolian propolis extract (PE) on colorectal cancer (CRC)using in vitro and in vivo studies. We exposed luciferase-transfected (Lovo-Luc CRC) cells and healthy colon cells (CCD-18Co) to varying concentrations of 5-FU and PE to assess their genotoxic, apoptotic, and cytotoxic effects, as well as their intracellular reactive oxygen species (iROS) levels. We also developed a xenograft model in nude mice and evaluated the anti-tumor effects of PE and 5-FU using various methods. Our findings showed that the combination of PE and 5-FU had selectivity against cancer cells, particularly at higher doses, and enhanced the anti-tumor effectiveness of 5-FU against colon CRC. The results suggest that PE can reduce side effects and increase the effectiveness of 5-FU through iROS generation in a dose-dependent manner. 相似文献
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Orhan Dengiz Ridvan Kizilkaya Aylin Erkocak Murat Durmus 《Geomicrobiology journal》2013,30(2):100-107
The main objective of this study was to determine changes in microbial response in natural soil aggregates for soil characterization in different fluvial land shapes. This study was carried out in fluvial lands formed on accumulated sediment depositions carried by K?z?l?rmak River. The majority soils of the study area were classified as Typic Ustifluvent and Typic Haplustept in Soil Taxonomy. It was found that macroaggregates (especially >6300 μm and 2000–4750 μm diameters) of all soil samples were higher than microaggregate of soils. In addition, it was determined that the Corg content varies between 0.41–0.91% in soil samples. Cmic content was also found higher level in aggregates involved <250 and 250–425 μm diameters as compared to other aggregate size classes. Moreover, we detected that Corg:Cmic ratio was much higher in macroaggregates than in microaggregate fractions. BR levels were also greater in macroaggregates of >6,300, 4,750–6,300 and 2,000–4,750 μm than in the other macroaggregates sizes and microaggregates. Consequently, macroaggregates have relatively more Corg level than the Corg level in microaggregates, even if the absolute values of Cmic were the lower. This study thus evidenced contrasting microbial habitats and their response in different soil aggregate size formed in various developed soils. 相似文献
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Gamze Guney Eskiler Isil Ezgi Eryilmaz Beste Yurdacan Unal Egeli Gulsah Cecener Berrin Tunca 《Journal of biochemical and molecular toxicology》2019,33(8)
The aim of this study was to investigate the combined effects of usnic acid (UA) and Tamoxifen (Tam) or Enzalutamide (Enz) on hormone receptor‐positive breast and prostate cancer (BC and PC), respectively. The antiproliferative and apoptotic effects of Tam or Enz alone and in combination with UA on MCF7 and LNCaP cancer cells were detected. The results of the WST‐1 assay indicated that UA was a promising anticancer compound that significantly enhanced the effectiveness of hormone therapy drugs compared with each drug alone (combination index < 1). In addition, the combination of UA with Tam or Enz remarkably induced more cell cycle arrest at the G0/G1 phase and apoptosis than only drug‐treated cells (P < 0.01). Consequently, our findings suggest that the combination of UA with Tam or Enz may be a potential therapeutic approach for the treatment of BC and PC and further studies are required to exploit the potential mechanisms of synergistic effects. 相似文献
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Ezgi Kunttas-Tatli Ryan A. Von Kleeck Bradford D. Greaves David Vinson David M. Roberts Brooke M. McCartney 《Molecular biology of the cell》2015,26(24):4503-4518
The tumor suppressor Adenomatous polyposis coli (APC) plays a key role in regulating the canonical Wnt signaling pathway as an essential component of the β-catenin destruction complex. C-terminal truncations of APC are strongly implicated in both sporadic and familial forms of colorectal cancer. However, many questions remain as to how these mutations interfere with APC’s tumor suppressor activity. One set of motifs frequently lost in these cancer-associated truncations is the SAMP repeats that mediate interactions between APC and Axin. APC proteins in both vertebrates and Drosophila contain multiple SAMP repeats that lack high sequence conservation outside of the Axin-binding motif. In this study, we tested the functional redundancy between different SAMPs and how these domains are regulated, using Drosophila APC2 and its two SAMP repeats as our model. Consistent with sequence conservation–based predictions, we show that SAMP2 has stronger binding activity to Axin in vitro, but SAMP1 also plays an essential role in the Wnt destruction complex in vivo. In addition, we demonstrate that the phosphorylation of SAMP repeats is a potential mechanism to regulate their activity. Overall our findings support a model in which each SAMP repeat plays a mechanistically distinct role but they cooperate for maximal destruction complex function. 相似文献
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Expression analysis of the novel gene collagen triple helix repeat containing-1 (Cthrc1) 总被引:2,自引:0,他引:2
Durmus T LeClair RJ Park KS Terzic A Yoon JK Lindner V 《Gene expression patterns : GEP》2006,6(8):935-940
We recently identified collagen triple helix repeat containing-1 (Cthrc1) as a novel gene induced in adventitial fibroblasts after arterial injury. Cthrc1 is a 30 kDa secreted protein that has the ability to inhibit collagen matrix synthesis. Cthrc1 is also glycosylated and retains a signal sequence consistent with the presence of Cthrc1 in the extracellular space. In injured arteries and skin wounds, we have found Cthrc1 expression to be associated with myofibroblasts and sites of collagen matrix deposition. Furthermore, we demonstrated that Cthrc1 inhibits collagen matrix deposition in vitro. Using in situ hybridization and immunohistochemistry, we characterized the expression domains of Cthrc1 during murine embryonic development and in postnatal tissues. In mouse embryos, Cthrc1 was expressed in the visceral endoderm, notochord, neural tube, developing kidney, and heart. Abundant expression of Cthrc1 was observed in the developing skeleton, i.e., in cartilage primordia, in growth plate cartilage with exclusion of the hypertrophic zone, in the bone matrix and periostium. Bones from adults showed expression of Cthrc1 only in the bone matrix and periostium while the articular cartilage lacked expression. Cthrc1 is typically expressed at epithelial-mesenchymal interfaces that include the epidermis and dermis, basal corneal epithelium, airway epithelium, esophagus epithelium, choroid plexus epithelium, and meninges. In the adult kidney, collecting ducts and distal tubuli expressed Cthrc1. Collectively, the sites of Cthrc1 expression overlap considerably with those reported for TGF-beta family members and interstitial collagens. The present study provides useful information towards the understanding of potential Cthrc1 functions. 相似文献
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Mefenamic acid, a non-steroidal antiinflammatory drug (NSAID), directly and dose-dependently exhibits neuroprotective activity. In our study, we investigated the effects of mefenamic acid against d-serine on oxidative stress in the hippocampus, cortex and cerebellum of rats. Furthermore, the potential inflammatory and apoptotic effects of d-serine and potential protective effect of mefenamic acid were determined at mRNA and protein levels of TNF-α, IL-1β, Bcl-2 and Bax. We found that d-serine significantly increased oxidative stress, levels of inflammation- and apoptosis-related molecules in a region specific manner. Mefenamic acid treatment provided significant protection against the elevation of lipid peroxidation, protein oxidation, levels of TNF-α, IL-1β and Bax. As a conclusion, we suggest that d-serine, as a potential neurodegenerative agent, may have a pivotal role in the regulation of oxidative stress, inflammation and apoptosis; and NSAIDs, such as mefenamic acid, may assist other therapeutics in treating disorders where d-serine-induced neurotoxic mechanisms are involved in. 相似文献
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Galluzzi L Vicencio JM Kepp O Tasdemir E Maiuri MC Kroemer G 《Current molecular medicine》2008,8(2):78-91
Macroautophagy (commonly referred to as autophagy) is the process by which intact organelles and/or large portions of the cytoplasm are engulfed within double-membraned autophagic vacuoles for degradation. Whereas basal levels of autophagy ensure the physiological turnover of old and damaged organelles, the massive accumulation of autophagic vacuoles may represent either an alternative pathway of cell death or an ultimate attempt for cells to survive by adapting to stress. The activation of the autophagic pathway beyond a certain threshold may promote cell death directly, by causing the collapse of cellular functions as a result of cellular atrophy (autophagic, or type II, cell death). Alternatively, autophagy can lead to the execution of apoptotic (type I) or necrotic (type III) cell death programs, presumably via common regulators such as proteins from the Bcl-2 family. On the other hand, limited self-eating can provide cells with metabolic substrates to meet their energetic demands under stressful conditions, such as nutrient deprivation, or favor the selective elimination of damaged (and potentially dangerous) organelles. In these instances, autophagy operates as a pro-survival mechanism. The coordinate regulation of these opposite effects of autophagy relies upon a complex network of signal transducers, most of which also participate in non-autophagic signaling cascades. Thus, autophagy occupies a crucial position within the cell's metabolism, and its modulation may represent an alternative therapeutic strategy in several pathological settings including cancer and neurodegeneration. Here, we present a general outline of autophagy followed by a detailed analysis of organelle-specific autophagic pathways and of their intimate connections with cell death. 相似文献