Yazar "Doganlar, Zeynep B." seçeneğine göre listele

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    The Comparison of the Perceived Exertion of Physically Active and Non-Active Men During High Intensity Cycling Intervals
    (Wiley, 2018) Vardar, Selma A.; Doganlar, Zeynep B.; Kaya, Oktay; Tayfur, Pinar; Sut, Necdet; Merakli, Meryem A.; Doganlar, Oguzhan
    [Abstract Not Available]
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    The flavonoid apigenin reduces prostate cancer CD44+ stem cell survival and migration through PI3K/Akt/NF-?B signaling
    (Pergamon-Elsevier Science Ltd, 2016) Erdogan, Suat; Doganlar, Oguzhan; Doganlar, Zeynep B.; Serttas, Riza; Turkekul, Kader; Dibirdik, Ilker; Bilir, Ayhan
    Aims: Cancer stem cells (CSCs) are involved in drug resistance, metastasis and recurrence of cancers. The efficacy of apigenin on cell survival, apoptosis, migration and stemness properties were analyzed in CSCs. Main methods: Prostate CSCs (CD44(+)) were isolated from human prostate cancer (PCa) PC3 cells using a magnetic-activated cell sorting system. PC3 and CSCs were treated with various concentrations of apigenin, docetaxel and their combinations for 48 h. Key findings: Apigenin dose dependently inhibited CSCs and PC3 cell survival, and this was accompanied with a significant increase of p21 and p27. Apigenin induced apoptosis via an extrinsic caspase-dependent pathway by upregulating the mRNA expressions of caspases-8,-3 and TNF-alpha, but failed to regulate the intrinsic pathway as determined by the Bax, cytochrome c (Cyt-c) and APAF-1 in CSCs. In contrary to CSCs, apigenin induced intrinsic apoptosis pathway as evidenced by the induction of Bax, Cyt-c and caspase-3 while caspase-8, TNF-alpha and Bcl-2 levels remained unchanged in PC3 cells. The flavonoid strongly suppressed the migration rate of CSCs compared to untreated cells. Significant downregulation of matrix metallopeptidases-2,-9, Snail and Slug exhibits the ability of apigenin treatment to suppress invasion. The expressions of NF-kappa B p105/p50, PI3K, Akt and the phosphorylation of pAkt were decreased after apigenin treatment. Moreover, apigenin treatment significantly reduced pluripotency marker Oct3/4 protein expression which might be associated with the down-regulation of PI3K/Akt/NF-kappa B signaling. Significance: Our data indicated that, apigenin could be a useful compound to prevent proliferation and migration of cancer cells as well as CSCs. (C) 2016 Elsevier Inc. All rights reserved.
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    Inhibition of Midkine Suppresses Prostate Cancer CD133+ Stem Cell Growth and Migration
    (Elsevier Science Inc, 2017) Erdogan, Suat; Doganlar, Zeynep B.; Doganlar, Oguzhan; Turkekul, Kader; Serttas, Riza
    Background: Midkine (MDK) is a tumor-promoting factor that is often overexpressed in various human carcinomas, and the role of MDK has not yet been fully investigated in prostate cancer stem cells. Materials and Methods: Prostate cancer CD133(+) stem cells (PCSCs) were isolated from human castration-resistant PC3 cells. PCSCs were treated with different concentrations of MDK inhibitor, iMDK, for 24-72 hours. The IC50 values were determined by the MTT test. Endogenous MDK messenger RNA expression was knocked down by small interfering RNA. Quantitative reverse transcription polymerase chain reaction, Western blot analyses and image-based cytometry were used to investigate apoptosis and cell cycle progression as well as their underlying molecular mechanisms. Cell migration was evaluated by the wound healing test. Results: iMDK caused dose- and time-dependent inhibition of PCSC survival. Similar growth inhibition was also obtained by small interfering RNA mediated knockdown of endogenous MDK expression. iMDK was shown to preferentially induce cell cycle arrest at the S and G2/M phases. Suppressed PCSC growth was also accompanied by increases in p53 and the cell cycle inhibitor p21 genes. Combinatorial treatment of iMDK with docetaxel significantly inhibited cell proliferation versus either of the agents used alone. Inhibition of MDK expression strongly suppressed the migration of PCSCs compared to untreated and docetaxel-treated cells. iMDK and the knockdown of MDK decreased p-Akt and significantly upregulated the expression of PI3K/phosphatase/tensin homolog. Conclusions: Our data indicate that MDK plays a crucial role in controlling PCSC proliferation and migration. Therefore, suppression of endogenous expression of MDK would, in combination with traditional chemotherapy drugs, be a potential treatment for PCSCs.
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    Midkine downregulation increases the efficacy of quercetin on prostate cancer stem cell survival and migration through PI3K/AKT and MAPK/ERK pathway
    (Elsevier France-Editions Scientifiques Medicales Elsevier, 2018) Erdogan, Suat; Turkekul, Kader; Dibirdik, Ilker; Doganlar, Oguzhan; Doganlar, Zeynep B.; Bilir, Ayhan; Oktem, Gulperi
    Aims: To examine the functions of growth factor midkine (MK) and a flavonoid quercetin on survival, apoptosis and migration of prostate cancer (PCa) stem cells (CSCs). Main methods: CD44(+)/CD133(+) and CD44(+) stem cells were isolated from PC3 and LNCaP cells, respectively by magnetic-activated cell sorting system. 3D cell culture was used to evaluate the ability of quercetin, MK siRNA, and the combination of both to inhibit spheroid formation, apoptosis and cell cycle arrest. Image-based cytometer, RT-qPCR, Western blotting and transwell migration assays were performed. Key findings: Quercetin treatment for 24-72 h inhibited PC3 and CD44+/CD133+ stem cell proliferation in a time-and dose-dependent manner. Knockdown of endogenous MK expression significantly suppressed proliferation of CD44(+)/CD133(+) and CD44(+) cells as well as their parent cells. Co-administration of MK siRNA and quercetin reduced the cell survival, induced apoptosis and caused G1 phase cell cycle arrest more effectively than the individual therapy. Knockdown of MK significantly enhanced the inhibitory effect of quercetin on CD44(+)/CD133(+) migration and spheroid formation. In addition, the combined therapy inhibited the phosphorylation of PI3K, AKT and ERK1/2, and reduced the protein expression of p38, ABCG2 and NF-kappa B. Significance: Quercetin alone exhibited significant cytotoxic effects on CD44(+)/CD133(+). MK plays an important role in the proliferation of CD44(+)/CD133(+) and CD44(+) cells in particular, and quercetin and MK-silencing therapy may be an important strategy in targeting CSCs that play a role in relapse, migration and drug resistance.
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    Midkine silencing enhances the anti-prostate cancer stem cell activity of the flavone apigenin: cooperation on signaling pathways regulated by ERK, p38, PTEN, PARP, and NF-?B
    (Springer, 2020) Erdogan, Suat; Turkekul, Kader; Dibirdik, Ilker; Doganlar, Zeynep B.; Doganlar, Oguzhan; Bilir, Ayhan
    Prostate cancer (PCa) is the most common cancer in men worldwide. Midkine (MK) is overexpressed in PCa, as well as in tumor-initiating cells termed cancer stem cells (CSCs). Apigenin is a dietary flavone with considerable anti-tumor activities. In this study, we explored the possible therapeutic use of MK silencing, apigenin treatment, and a combination of both on human PCa and prostate cancer stem cells (PCSCs). CD44(+)CD133(+) PC3 and CD44(+) LNCaP CSCs were isolated from their parent cell lines. Both MK knockdown and apigenin treatment resulted in loss of cell viability in PCSCs, and these effects were significantly elevated when apigenin was applied with MK silencing. Combined treatment of CD44(+)CD133(+) PC3 cells with apigenin and MK siRNA was also more effective in inducing apoptotic and non-apoptotic cell death when compared with individual applications. Treatment of CD44(+) LNCaP cells with apigenin significantly decreased viability, although the combination treatment did not markedly alter the individual therapy. Molecular events underlying cell cycle arrest and inhibition of the survival, proliferation, and migration of CD44(+)CD133(+) PC3 cells were found to be associated with upregulated p21, p27, Bax, Bid, caspase-3, and caspase-8 expression, as well as downregulated p-p38, p-ERK, NF-kappa B, and PARP. In addition, the combination of apigenin treatment and MK silencing showed better outcomes on the anticancer efficacy of docetaxel in CD44(+)CD133(+) PC3 cells. In conclusion, MK-regulated events are different between PCSCs, and when combined with apigenin plus MK silencing, docetaxel treatment may be a valuable approach for the eradication of PCSCs.
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    Naringin sensitizes human prostate cancer cells to paclitaxel therapy
    (Elsevier, 2018) Erdogan, Suat; Doganlar, Oguzhan; Doganlar, Zeynep B.; Turkekul, Kader
    Background: The aim of the study was to evaluate whether the use of chemotherapy in combination with naringin, a dietary plant polyphenolic flavonoid, could enhance the therapeutic efficacy of paclitaxel treatment in human prostate cancer (PCa) cells. Materials and methods: DU145, PC3, and LNCaP cells were treated with various concentrations of paclitaxel, naringin, and their combinations. Methylthiazolyldiphenyl-tetrazolium bromide (MTT), image-based cytometer, quantitative reverse transcription PCR (RT-qPCR), Western blot, and transwell assay were used to evaluate cell viability, apoptosis and cell cycle, the mRNA expression, protein expression, and cell migration, respectively. Results: Naringin treatment inhibited cell survival in a dose- and time-dependent manner by inducing apoptosis and cell cycle arrest in G1 phase. Among the pathways evaluated, naringin (150 mu M) significantly induced the mRNA expressions of BAX, BID, caspase 3, cytochrome c, p53, p21(Cip1), and p27(Kip1) and down-regulated the expressions of survivin and livin in DU145 cells. The combination of naringin and paclitaxel treatments synergistically increased the cytotoxic effects of paclitaxel in androgen-independent DU145 and PC3 cells, as well as in androgen-sensitive LNCaP cells. The combination of naringin with docetaxel has almost the same inhibitory effect on cell proliferation as the paclitaxel combination in androgen-independent cells, whereas there is no similar effect in LNCaP cells. Naringin exhibits significant inhibitory effects on the cell migration ability. The flavonoid either alone or in combination with paclitaxel therapy resulted in an increase in tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) protein expression and decrease in nuclear factor-kB p50 protein level in DU145 cells. Conclusion: In conclusion, naringin acts as a chemosensitizer which synergistically strengths the cytotoxic effect of paclitaxel in PCa cells. Therefore, naringin therapy alone or in combination with paclitaxel may be useful in the treatment of PCa. However, there is a need for more detailed in vivo studies of the mechanism of action. (C) 2017 Asian Pacific Prostate Society, Published by Elsevier Korea LLC.