Browsing by Author "Semiz, Asli"

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Citation - WoS: 20
Citation - Scopus: 23
Suppression of Inflammatory Cytokines Expression With Bitter Melon (Momordica Charantia) in TNBS-Instigated Ulcerative Colitis
(Sciendo, 2020) Semiz, Asli; Acar, Ozden Ozgun; Cetin, Hulya; Semiz, Gurkan; Sen, Alaattin
Background and Objective: This study was aimed to elucidate the molecular mechanism of Momordica charantia (MCh), along with a standard drug prednisolone, in a rat model of colitis induced by trinitrobenzene sulfonic acid (TNBS). Methods: After the induction of the experimental colitis, the animals were treated with MCh (4 g/kg/day) for 14 consecutive days by intragastric gavage. The colonic tissue expression levels of C-C motif chemokine ligand 17 (CCL-17), interleukin (IL)-1 beta, IL-6, IL-23, interferon-gamma (IFN-gamma), nuclear factor kappa B (NFkB), and tumor necrosis factor-alpha (TNF-alpha), were determined at both mRNA and protein levels to estimate the effect of MCh. Besides, colonic specimens were analyzed histopathologically after staining with hematoxylin and eosin. Results: The body weights from TNBS-instigated colitis rats were found to be significantly lower than untreated animals. Also, the IFN-gamma, IL-1 beta, IL-6, Il-23, TNF-alpha, CCL-17, and NF-kB mRNA and protein levels were increased significantly from 1.86-4.91-fold and 1.46-5.50-fold, respectively, in the TNBS-instigated colitis group as compared to the control. Both the MCh and prednisolone treatment significantly reduced the bodyweight loss. It also restored the induced colonic tissue levels of IL-1 beta, IL-6, IFN-gamma, and TNF-alpha to normal levels seen in untreated animals. These results were also supported with the histochemical staining of the colonic tissues from both control and treated animals. Conclusion: The presented data strongly suggests that MCh has the anti-inflammatory effect that might be modulated through vitamin D metabolism. It is the right candidate for the treatment of UC as an alternative and complementary therapeutics.
Citation - WoS: 13
Citation - Scopus: 12
Role of AHR, NF-kB and CYP1A1 Crosstalk With the X Protein of Hepatitis B Virus in Hepatocellular Carcinoma Cells
(Elsevier, 2023) Celik-Turgut, Gurbet; Olmez, Nazmiye; Koc, Tugba; Ozgun-Acar, Ozden; Semiz, Asli; Dodurga, Yavuz; Sen, Alaattin
In this study, it was aimed to elucidate the interaction between aryl hydrocarbon receptor (AHR), nuclear factor -kappa B (NF-kB), and cytochrome P4501A1 (CYP1A1) with hepatitis B virus X protein (HBX) in a human liver cancer cell line (HepG2) transfected with HBX. First, AHR, NF-kB, and CYP1A1 genes were cloned into the appropriate region of the CheckMate mammalian two-hybrid recipient plasmids using a flexi vector system. Renilla and firefly luciferases were quantified using the dual-luciferase reporter assay system to measure the interactions. Secondly, transient transfections of CYP1A1 and NF-kB (RelA) were performed into HBX-positive and HBX-negative HepG2 cells. The mRNA expression of CYP1A1 and NF-kB genes were confirmed with RT-PCR, and cell viability was measured by WST-1. Further verification was assessed by measuring the activity and protein level of CYP1A1. Additionally, CYP1A1/HBX protein-protein interactions were performed with co-immunoprecipitation, which demonstrated no interaction. These results have clearly shown that the NF-kB and AHR genes interact with HBX without involving CYP1A1 and HBX protein-protein interactions. The present study confirms that AHR and NF-kB interaction plays a role in the HBV mechanism mediated via HBX and coordinating the carcinogenic or inflammatory responses; still, the CYP1A1 gene has no effect on this interaction.
Apatinib Sensitizes Human Breast Cancer Cells Against Navitoclax and Venetoclax Despite Up-Regulated Bcl-2 and Mcl-1 Gene Expressions
(Kare Publ, 2021) Kavakcioglu Yardimci, Berna; Ozgun Acar, Ozden; Semiz, Asli; Sen, Alaattin
OBJECTIVE Defects in apoptotic cell death which restrict the success of conventional cytotoxic therapies have pivotal roles in a number of pathological conditions including cancer. However, a novel drug class targeting pro-survival Bcl-2 protein family members has been developed with the understanding of the structures and interactions of Bcl-2 proteins. Within this new class, Bcl-2/Bcl-xL inhibitor Navitoclax and Bcl-2 specific inhibitor Venetoclax have been shown to demonstrate strong anticancer activities on several types of cancers. But their low affinity to other anti-apoptotic proteins limits their clinical usage. Here, we investigated the cytotoxic and apoptotic effects of Navitoclax/Venetoclax and their combinations with specific tyrosine kinase inhibitor Apatinib on estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cell lines. METHODS MTT assay was used for the evaluation of the inhibition of cancer cell proliferation. ELISA test and Quantitative real-time PCR assay was performed to determine the role of caspase-3, Bak, Bax, Bcl-2, Bcl-xL and Mcl-1 proteins in the inhibition of cell proliferation triggered by the tested agents. RESULTS We found that aggressive MDA-MB-231 cell line was more sensitive to all tested agents. Apatinib significantly enhanced Navitoclax/Venetoclax mediated inhibition of cell viability in both cancer cell lines despite up-regulation in the expression levels of Bcl-2 and Mcl-1 genes. We further demonstrated significant Bak/Bax and caspase-3 expression in less aggressive MCF-7 cells. CONCLUSION Our findings have impacts on Navitoclax/Venetoclax plus Apatinib based therapy for breast adenocarcinoma. On the other hand, further studies should be conducted to elucidate the mechanisms underlying synergistic effects of Navitoclax/Venetoclax plus Apatinib combinations.