Yazar "Azzawri, Ali Ahmed" seçeneğine göre listele

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  • Küçük Resim
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    Expression of GRP78 and its copartners in HEK293 and pancreatic cancer cell lines (BxPC-3/PANC-1) exposed to MRI and CT contrast agents
    (Taylor and Francis Ltd., 2023) Azzawri, Ali Ahmed; Yıldırım, İbrahim Halil; Yeğin, Zeynep; Duşak, Abdürrahim
    Endoplasmic reticulum (ER) stress-associated chaperones trigger a defense mechanism called as unfolded protein response (UPR) which can manage apoptosis and be determinative in cell fate. Both anticancer drug effects and potential toxicity effects of magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents were aimed to be evaluated. For this purpose, we investigated expression profiles of endoplasmic reticulum stress-associated chaperone molecules in human pancreatic tumor lines BxPC-3 and PANC-1 and control human embryonic kidney cells 293 (HEK293) induced with a variety of gadolinium and iohexol contrast agents. Protein expression levels of ER stress-associated chaperones (master regulator: GRP78/Bip and its copartners: Calnexin, Ero1, PDI, CHOP, IRE1α and PERK) were evaluated with Western blotting. Expression levels at mRNA level were also assessed for GRP78/Bip and CHOP with real-time PCR. Induction of cells was carried out with four different Gd-based contrast agents (GBCAs): (Dotarem, Optimark, Primovist and Gadovist) and two different iohexol agents (Omnipol, Omnipaque). CT contrast agents tested in the study did not result in significant ER stress in HEK293 cells. However, they do not seem to have theranostic potential in pancreas cancer through ER pathway. The potential efficiency of macrocyclic MRI contrast agents to provoke apoptosis via ER stress-associated chaperones in BxPC-3 cells lends credibility for their future theranostic use in pancreas cancer as long as undesired toxicity effects were carefully considered. ER stress markers and/or contrast agents seem to have promising potential to be translated into the clinical practice to manage pancreas cancer progression.
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    Small molecule inhibitor of nicotinamide N-methyltransferase shows anti-proliferative activity in HeLa cells
    (Taylor & Francis, 2021) Akar, Serra; Duran, Tuğçe; Azzawri, Ali Ahmed; Koçak, Nadir; Çelik, Çetin; Yıldırım, Halil İbrahim
    The anti-proliferative effects of 5-methylquinolinium (5MQ) of nicotinamide N-methyltransferase (NNMT) have not been previously investigated on a cervical cancer cell line. NNMT is a metabolic enzyme that is correlated with tumour progression and metastasis. 5MQ is a small molecule inhibitor of NNMT. 0.1-500 mu M of 5MQ was tested on the HeLa epithelial cervical cancer cell line. Cell viability was assessed with the MTT test. TWIST, ZEB1, SERPIN1, SIRT1, CD16, mRNA and various protein expression levels were analysed with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western Blotting, respectively. 5MQ significantly inhibited HeLa cell proliferation in a concentration and time-dependent manner. Increased cell shrinkage, loss of cellular adhesions and apoptotic bodies were observed in HeLa cells after 5MQ treatment. Following treatment with 5MQ, ZEB1, SIRT1, CD16 mRNA levels were increased while TWIST and SERPIN1 mRNA levels were reduced. Expressions of oncogenic proteins phospho-Akt and SIRT1 were decreased. 5MQ can effectively inhibit HeLa cell proliferation without apparently affecting HEK-293 cell proliferation. IMPACT STATEMENT What is already known on this subject? NNMT is a cytosolic enzyme involved in tumour progression, metastasis and treatment resistance. It was overexpressed in many human malignancies. 5-amino-1-methylquinolinium (5MQ) is a novel small molecule inhibitor of NNMT that has shown promising results in the treatment of obesity and in senescent muscle regeneration. 5MQ has not been tested on the HeLa cervical cancer cell line, previously. What do the results of this study add? In this study, 5MQ was tested on the HeLa cervical cancer cell line for the first time and the molecular changes associated with 5MQ treatment were analysed. 5MQ demonstrated significant anti-proliferative activity on HeLa cells, which displayed morphological signs of apoptosis. Treatment of HeLa cells with 5MQ led to an increase in ZEB1, SIRT1 mRNA while TWIST mRNA was decreased. Phospho-Akt and Sirtuin1 protein expressions were decreased. What are the implications of these findings for clinical practice and/or further research? 5MQ can effectively inhibit HeLa cell proliferation without apparently affecting HEK-293 cell proliferation. 5MQ treatment was associated with a decrease in the expression of phospho-Akt and Sirtuin1 proteins, both of which have been reported to maintain tumour progression. 5MQ can further be investigated and modified for anti-cancer therapy.
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    Thymoquinone induces apoptosis via targeting the Bax/BAD and Bcl-2 pathway in breast cancer cells
    (2019) Duran, Tuğçe; Azzawri, Ali Ahmed; Yıldırım, İbrahim Halil
    Objective: Nigella sativa, commonly known as the black seed, has been used since ancient times in folk medicine, andits various therapeutic benefits have been mentioned in some ancient medical sources and confirmed by modernscience. Thymoquinone is the major compound and essential active ingredient of Nigella sativa seed oil.Thymoquinone has been reported to have high biological activity and broad therapeutic potential through severalmechanisms that affect cells including anti-oxidant, anti-inflammatory, and anti-tumor properties. Although it hasbeen widely reported that Thymoquinone inhibits cell growth and proliferation and stimulates apoptosis in varioustypes of cancer cells, the mechanisms and signaling pathways are not fully understood. The aim of this study was todetermine the effect of Thymoquinone on apoptosis in both tumor and non-tumor cells.Methods: In this study, breast cancer cell line (MCF-7) was used as tumor cells and Human Embryonic Kidney Cell line(HEK293) was used as non-tumor cells. Cells were treated with Thymoquinone and viability test performed by MTTassay.Gene expression of apoptosis markers such as Bax, BAD, Bcl-2, and p53 was determined by Real-Time PCR.HEK293 cells were used as non-tumor control.Results and Conclusion: Results suggest that Thymoquinone has a strong effect on cell proliferation and vitality.Thymoquinone has increased the expression of BAD, Bax genes which induce apoptosis and decreased the p53 gene inbreast cancer cells. Therefore Thymoquinone promotes apoptosis and enhances anti-cancer efficacy in breast cancercells.