Mercanoglu, G. | Safran, N. | Gungor, M. | Pamukcu, B. | Uzun, H. | Sezgin, C. | Fici, F.

Article | 2008 | Circulation Journal72 ( 4 ) , pp.660 - 670

Background: In the present study, nitric oxide (NO) was investigated to see if it mediated effects of nebivolol on apoptosis in the rat myocardial infarction (MI) model. Methods and Results: Rats were divided into 3 groups: sham operated (sham-control), MI-induced (MI-control) and nebivolol treated (MI-nebivolol). The initial dose of nebivolol was administrated intravenously (iv) within 10min of post-MI reperfusion and continued orally for 28 days. NO mediated effects of nebivolol were assessed either in the early (2nd day) or sub-acute (28th day) period of MI by histologic, hemodynamic and biologic studies. Left ventricular (LV) pr . . .essure changes were prevented with nebivolol (the increase in LV end-diastolic pressure and the decrease in maximum rise and fall rate of LV pressure (+dp/dt and -dp/dt) was significantly less in MI-nebivolol). Total and regional apoptotic indexes were significantly lower in the MI-nebivolol group (10.2 vs 7.1%, respectively on the 2 nd day; p=0.004). Although plasma nitrite/nitrate, cyclic guanylate cyclase and peroxynitrite concentrations were high both in Mi-control and MI-nebivolol groups on the 2nd day, these concentrations were decreased to the basal value on the 28th day in the MI-nebivolol group. Conclusion: As a result, nebivolol treatment (initially by iv within 10min of reperfusion and continued orally) reduced the myocardial apoptosis after MI. This beneficial effect of nebivolol is mediated by NO regulation Daha fazlası Daha az

Yenigun, V.B. | Ozpolat, B. | Torun Kose, G.

Article | 2013 | International Journal of Molecular Medicine31 ( 6 ) , pp.1477 - 1483

The cancer stem cell hypothesis emphasizes that cancers are driven by cells having stem cell properties, and it is believed that cancer stem cells (CSCs) may be responsible for resistance against therapeutic approaches and for recurrent tumors. Since the biology of the normal breast requires large numbers of stem cells, it has been thought that breast stem cells play an important role in initiating breast cancer. A better characterization of breast CSCs appears to be an essential step to improve the understanding of the biology of breast cancer and its management. The scope of this study was to isolate breast CSCs from a breast canc . . .er cell line (MCF-7) using cell surface markers, and to test whether these cells have any resistance to autophagic cell death mechanisms mediated by commonly used chemotherapies and hormonal therapies such as doxorubicin (adriamycin) and tamoxifen (anti-estrogen), respectively. For this purpose, the CD44+/CD24-/lowMCF-7 breast cancer stem/progenitor cell population was isolated and treated with doxorubicin or tamoxifen and evaluated for their response to growth, autophagy and apoptosis. Our findings suggest that CD44+/CD24-/lowcells were less sensitive to doxorubicin, but did not demonstrate a significant difference towards tamoxifen in regards to the induction of autophagy Daha fazlası Daha az

Aydemir, EA | Simsek, E | Imir, N | Gokturk, RS | Yesilada, E | Fiskin, K

Article | 2015 | PHARMACOGNOSY MAGAZINE11 ( 42 ) , pp.1477 - 1483

Background: Fabaceae family members are known to possess preventive and therapeutic potentials against various types of cancers. Objective: The aim of this study was to investigate the cytotoxic and apoptotic effects of hydroalcoholic extracts from the aerial parts and roots of an endemic Ebenus species; Ebenus boissieri Barbey in human lung cancer cell line. Materials and Methods: After treatment with hydroalcoholic extracts cytotoxic activities of both extracts were measured by 3-(4, 5-dimethylthiazolyl-2) -2,5-diphenyltetrazolium bromide assay, whereas caspase-3 activity, tumor necrosis factor-alpha (TNF-alpha) and interferon gam . . .ma (IFN-gamma) release were measured by enzyme linked immunosorbent assay. Results: According to in vitro assay results, the increase in all caspases activity suggested that extracts induce cells to undergo apoptosis. Especially, induction in caspase-3 activity was the most remarkable result of this study. Both aerial part and root extracts induced apoptosis by increasing caspase-3 activity, TNF-alpha and IFN-gamma release. When compared to their relative controls, the concentrations of both TNF-alpha and IFN-gamma in extract-treated groups were signi.cantly and dose dependently exalted. Conclusion: Taken together, our results indicate that the hydroalcoholic extracts of E. boissieri can be considered as a source of new anti-apoptotic and therefore anti-carcinogenic agent Daha fazlası Daha az

Kalay, S. | Dogan, A. | Turkan, A. | Demiroglu-Zergeroglu, A.

Article | 2017 | Turkish Journal of Biochemistry42 ( 5 ) , pp.577 - 585

Aim: Impaired mitochondrial function is a consequence of HIF1-induced overexpression of pyruvate dehydrogenase kinase (PDK) which phosphorylates and inactivates pyruvate dehydrogenase multi-enzyme complex (PDC), which converts pyruvate to acetyl-CoA for entry into the TCA cycle. Shifting cancer cells from glycolysis to oxidative phosphorylation induces apoptosis, which is a new therapeutic strategy by utilizing PDK inhibitors. In this work, the effect of PDK inhibitor, dichloroacetate (DCA) has been investigated in Human renal carcinoma cell line. Methods: Adherent epithelium renal cell adenocarcinoma (ACHN) cells were treated with . . .different concentrations of DCA at different time periods. Cell viability was measured by WST assay, cell-cycle profile and apoptosis were assessed by using flow cytometry. Metabolites of the cell extracts were analyzed by LC-MS/MS. Results: DCA reduced cell viability in a concentration- and time-dependent manner. Treatment with DCA induced G1 arrest and apoptosis in ACHN cells. Additionally, metabolite changes of ACHN cell line upon DCA treatments showed that lactate, citrate, N-acetylaspartate and 5-oxoproline levels, which were high in untreated cells, significantly reduced upon DCA treatment. Conclusion: Potential anti-carcinogenic effects of DCA, including inhibition of cell proliferation and growth, and induction of apoptosis, as well as the ability of markedly reducing lactate levels make this agent a promising drug candidate in renal adenocarcinomas. © 2017, Turkish Biochemistry Society. All rights reserved Daha fazlası Daha az

Maroufi, N.F. | Vahedian, V. | Mazrakhondi, S.A.M. | Kooti, W. | Khiavy, H.A. | Bazzaz, R. | Sabzichi, M.

Article | 2020 | Naunyn-Schmiedeberg's Archives of Pharmacology393 ( 1 ) , pp.577 - 585

The harmful dose-dependent side effects of chemotherapy drugs have caused the discovery of novel perspective to evaluate chemotherapy protocols. In this study, the potential application of Compritol was investigated as a major scaffold into nanostructured lipid careers to highlight myricetin efficiency in treatment of breast cancer cells along with codelivery of docetaxel (DXT). Characterization of myricetin-loaded NLCs was carried out by measuring the particle size and zeta potential, using the scanning electron microscopy. MTT, DAPI staining, flow cytometric, and RT-PCR (real-time) assays were used to recognize novel formulation b . . .ehavior on cell cytotoxicity as well as recognizing molecular mechanism of formulation concerning apoptosis phenomenon. Myricetin-loaded NLCs reduced the cell viability from 50 ± 2.3 to 40 ± 1.3% (p < 0.05). Percentage of apoptosis improved with combination treatment of myricetin-loaded NLCs and DXT in the MDA-MBA231 breast cancer cells. Expression of antiapoptotic genes (survivin, Cyclin B1, and Mcl1) indicated a significant reduction in factor along with increment in proapoptotic factor Bax and Bid mRNA rates. Overall, our results represented that the NLC delivery system could be a promising strategy to enhance the effect of anticancer agents such as DXT on breast cancer. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature Daha fazlası Daha az

Verim, L. | Timirci-Kahraman, O. | Akbulut, H. | Akbas, A. | Ozturk, T. | Turan, S. | İşbir, Turgay

Article | 2014 | In Vivo28 ( 3 ) , pp.397 - 402

Background: The present study aimed to evaluate the role of functional polymorphisms of apoptosis-associated Fatty acid synthase (FAS) and fatty acid synthase ligand (FASL) genes in bladder cancer susceptibility as first presentation in a Turkish population. Patients and Methods: Genotypes of 91 patients with bladder cancer and 101 healthy controls were evaluated for the polymorphism of FAS-1377 G/A and FASL-844 T/C genes by polymerase chain reaction and restriction fragment length polymorphism analysis. Results: The frequency of the FAS-1377 G allele was significantly higher in patients with bladder cancer compared to controls (p

Ozdemir-Kumral, ZN | Erkek, BE | Karakus, B | Almaci, M | Fathi, R | Yuksel, M | Alican, I

Article | 2019 | JOURNAL OF SURGICAL RESEARCH243 , pp.165 - 172

Background: 1,25 Dihydroxyvitamin D-3 (1,25(OH)(2)D-3) modulates inflammation and immune responses. Deficiency of 1,25(OH)(2)D-3 was found to be associated with the risk of cancer, cardiovascular disease, osteoarthritis, infections, and autoimmune diseases. This study evaluated the effect of 1,25 dihydroxyvitamin D-3 1,25(OH)(2)D-3 on thioacetamide (TAA)-induced acute liver injury in rats. Materials and methods: Rats were treated with either saline or 1,25(OH)(2)D-3 (0.30 mg/kg; orogastrically) for 15 d. Starting from day 13, TAA (200 mg/kg; intraperitoneally) was given for 3 d. On day 15, all rats were euthanized. Liver and blood s . . .amples were collected. Results: TAA caused severe damage, increased lipid peroxidation with reductions in endogenous antioxidants, increased apoptosis, increased production of reactive oxygen species, and elevated inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-kappa B) expression in liver. Extent of damage was decreased by 1,25(OH)(2)D-3 (P < 0.01). 1,25(OH)(2)D-3 attenuated the increase in malondialdehyde (P < 0.01), increase in myeloper-oxidase (P < 0.01), increase in chemiluminescence levels (P < 0.05) and apoptotic activity (P < 0.001). Elevated liver iNOS and NF-kappa B expression in TAA group was also reduced by 1,25(OH)(2)D-3 (P < 0.001, for iNOS; P < 0.001, for NF-kappa B). TAA group revealed high serum aspartate transaminase and alanine transaminase (ALT) activities (P < 0.01, for aspartate transaminase; P = 0.08, for ALT) and reduced albumin levels (P < 0.01) compared with control. 1,25(OH)(2)D-3 had no statistically significant effect on these parameters. Conclusions: 1,25(OH)(2)D-3 provides protection against hepatic injury in a rat model of TAA-induced hepatotoxicity via suppression of inflammatory reaction, oxidative stress, and apoptosis. (C) 2019 Elsevier Inc. All rights reserved Daha fazlası Daha az

Attar, Rukset | Gasparri, M.L. | Di Donato, V. | Yaylim, I. | Halim, T.A. | Zaman, F. | Farooqi, A.A.

Article | 2014 | Asian Pacific Journal of Cancer Prevention15 ( 8 ) , pp.3359 - 3362

Increasing attention is being devoted to the mechanisms by which cells receive signals and then translate these into decisions for growth, death, or migration. Recent findings have presented significant breakthroughs in developing a deeper understanding of the activation or repression of target genes and proteins in response to various stimuli and of how they are assembled during signal transduction in cancer cells. Detailed mechanistic insights have unveiled new maps of linear and integrated signal transduction cascades, but the multifaceted nature of the pathways remains unclear. Although new layers of information are being added . . .regarding mechanisms underlying ovarian cancer and how polymorphisms in VDR gene influence its development, the findings of this research must be sequentially collected and re-interpreted. We divide this multi-component review into different segments: how vitamin D modulates molecular network in ovarian cancer cells, how ovarian cancer is controlled by tumor suppressors and oncogenic miRNAs and finally how vitamin D signaling regulates miRNA expression. Intra/inter-population variability is insufficiently studied and a better understanding of genetics of population will be helpful in getting a step closer to personalized medicine Daha fazlası Daha az

Yoğurtçu, B.M. | Demirci, S. | Doğan, A. | Asutay, A.B. | Şahin, Fikrettin

Article | 2017 | World Journal of Microbiology and Biotechnology33 ( 11 ) , pp.3359 - 3362

Invasive fungal infections are one of the major challenges especially for immunosuppressed patients since they are drug resistant and pathogen to patients. Therefore, developing new, efficient and nonresistant antifungal agents have been a primary focus of international research. In the current study, a novel Schiff base [hetero-dinuclear copper(II) Mn(II) complex] (SB) derivative was investigated for its anticandidal activity against Candida albicans and possible mechanisms inducing cell death. The results revealed that SB treatment induces apoptotic and necrotic pathways in C. albicans ATCC10231 strain. Intracellular reactive oxyg . . .en species production determined by 2',7'-dichlorofluorescein diacetate staining was triggered by SB and amphotericin B administrations in a dose-dependent manner. Gene expression analysis demonstrated that SB exposure resulted in regulation of critical development and stress related gene expressions. SB treatment directly upregulated expression of stress related genes, DDR48 and RIM101, while suppressed important cell signaling and antibiotic resistance acquiring related genes such as HSP90, ERG11 and EFG1. Furthermore, CaMCA1 mRNA levels were found to be significantly high in SB-treated yeast cells, indicating possible caspase-like mechanism activation. Scanning electron microscopy analysis confirmed that SB treatment led to severe cell wall integrity disruption and wrinkling. The study will encourage development of SB-based anticandidal regimens but further studies are highly warranted to understand limitations and the extended use in the routine. © 2017, Springer Science+Business Media B.V Daha fazlası Daha az

Shahwar, D. | Iqbal, M.J. | Nisa, M.-U. | Todorovska, M. | Attar, Rukset | Sabitaliyevich, U.Y. | Xu, B.

Review | 2019 | International Journal of Molecular Sciences20 ( 8 ) , pp.3359 - 3362

Rapidly developing resistance against different therapeutics is a major stumbling block in the standardization of therapy. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated signaling has emerged as one of the most highly and extensively studied signal transduction cascade that induces apoptosis in cancer cells. Rapidly emerging cutting-edge research has helped us to develop a better understanding of the signaling machinery involved in inducing apoptotic cell death. However, excitingly, cancer cells develop resistance against TRAIL-induced apoptosis through different modes. Loss of cell surface expression . . . of TRAIL receptors and imbalance of stoichiometric ratios of pro- and anti-apoptotic proteins play instrumental roles in rewiring the machinery of cancer cells to develop resistance against TRAIL-based therapeutics. Natural products have shown excellent potential to restore apoptosis in TRAIL-resistant cancer cell lines and in mice xenografted with TRAIL-resistant cancer cells. Significantly refined information has previously been added and continues to enrich the existing pool of knowledge related to the natural-product-mediated upregulation of death receptors, rebalancing of pro- and anti-apoptotic proteins in different cancers. In this mini review, we will set spotlight on the most recently published high-impact research related to underlying mechanisms of TRAIL resistance and how these deregulations can be targeted by natural products to restore TRAIL-mediated apoptosis in different cancers. © 2019 by the authors. Licensee MDPI, Basel, Switzerland Daha fazlası Daha az

Farooqi, A.A. | Wang, Z. | Hasnain, S. | Attar, Rukset | Aslam, A. | Mansoor, Q. | Ismail, M.

Note | 2015 | Asian Pacific Journal of Cancer Prevention16 ( 6 ) , pp.2575 - 2580

Cancer is a multifaceted and genomically complex disease and rapidly accumulating high impact research is deepening our understanding related to the mechanisms underlying cancer development, progression and resistance to therapeutics. Increasingly it is being realized that genetic/epigenetic mutations, inactivation of tumor suppressor genes, overexpression of oncogenes, deregulation of intracellular signaling cascades and loss of apoptosis are some of the extensively studied aspects. Confluence of information suggested that rapidly developing resistance to therapeutics is adding another layer of complexity and overwhelmingly increas . . .ing preclinical studies are identifying different natural agents with efficacy and minimal off-target effects. We partition this multi-component review into citrus fruits and their bioactive ingredients mediating rebalancing of pro- and anti-apoptotic proteins to induce apoptosis in resistant cancer cells. We also discuss how oncogenic protein networks are targeted in cancer cells and how these findings may be verified in preclinical studies Daha fazlası Daha az

Attar, Rukset | Tabassum, S. | Fayyaz, S. | Ahmad, M.S. | Nogueira, D.R. | Yaylim, I. | Ismail, M.

Article | 2015 | Cellular and Molecular Biology61 ( 6 ) , pp.62 - 68

Cancer is a multifaceted and genomically complex disease. Research over the years has gradually provided a near complete resolution of cancer landscape and it is now known that genetic/epigenetic mutations, inactivation of tumor suppressors, Overexpression of oncogenes, spatio-temporally dysregulated intracellular signaling cascades, epithelial to mesenchymal transition (EMT), metastasis and loss of apoptosis are some of the most extensively studied biological mechanisms that underpin cancer development and progression. Increasingly it is being realized that current therapeutic interventions are becoming ineffective because of tumor . . . heterogeneity and rapidly developing resistance against drugs. Considerable biological activities exerted by bioactive ingredients isolated from natural sources have revolutionized the field of natural product chemistry and rapid developments in preclinical studies are encouraging. Viscum album has emerged as a deeply studied natural source with substantial and multifaceted biological activities. In this review we have attempted to provide recent breakthroughs in existing scientific literature with emphasis on targeting of protein network in cancer cells. We partition this review into different sections, highlighting latest information from cell culture studies, preclinical and clinically oriented studies. We summarized how bioactive ingredients of Viscum album modulated extrinsic and intrinsic pathways in cancer cells. However, surprisingly, none of the study reported stimulatory effects on TRAIL receptors. The review provided in-depth analysis of how Viscum album modulated Endoplasmic Reticulum Stress in cancer cells and how bioactive chemicals tactfully targeted cytoskeletal machinery in cancer cells as evidenced by cell culture studies. It is noteworthy that Viscum album has entered into various phases of clinical trials, however, there are still knowledge gaps in our understanding regarding how various bioactive constituents of Viscum album modulate intracellular signaling cascades in cancer. Better and deeper comprehension oncogenic signaling cascades will prove to be helful in getting a step closer to individualized medicine. © 2015 Daha fazlası Daha az