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Öğe Apoptosis-mediated Cytotoxic Effects of Ibandronic Acid on Hormone- and Drug-refractory Prostate Cancer Cells and Human Breast Cancer Cells(Field House Publishing Llp, 2010) Kucukzeybek, Y.; Gorumlu, G.; Cengiz, E.; Karabulut, B.; Sezgin, C.; Atmaca, H.; Sanli, U. A.; Uzunoglu, S.; Uslu, R.Over 80% of patients with advanced breast and prostate cancer ultimately develop bone metastases. Ibandronic acid has proven efficacy for treatment of bone metastasis secondary to breast cancer. This study was designed to investigate the cytotoxic and apoptotic effects of ibandronic acid on hormone- and drug-refractory prostate carcinoma DU-145 and human breast cancer MCF-7 cell lines. Cytotoxicity was evaluated using an XTT cell proliferation kit, and apoptosis was assessed by enzyme-linked immunosorbent assay (histone-DNA fragmentation) and measurement of caspase 3/7 activity. With increasing concentrations of ibandronic acid there was a dose- and time-dependent decrease in cell numbers. MCF-7 cells were more resistant than DU-145 cells (half maximal inhibitory concentrations of 122 and 90 mu M, respectively). Ibandronic acid induced apoptosis in both cell lines. The study showed an apoptosis-mediated cytotoxic effect for ibandronic acid (in addition to the already known osteoclast inhibiting effect) in breast cancer patients with bone metastases; which was also observed in prostate cancer cells. Further clinical studies involving breast and prostate cancer patients with bone metastases are warranted to confirm these findings.Öğe AT-101 acts as anti-proliferative and hormone suppressive agent in mouse pituitary corticotroph tumor cells(Springer, 2018) Yurekli, B. S.; Karaca, B.; Kisim, A.; Bozkurt, E.; Atmaca, H.; Cetinkalp, S.; Ozgen, G.; Yilmaz, C.; Uzunoglu, S.; Uslu, R.; Saygili, F.Purpose Gossypol, a naturally occurring compound in cottonseeds, has anticancer effects against several tumor cell lines. It has been extensively studied in clinical trials and is well tolerated with a favorable safety profile. AT-101, a derivative of R (-)-gossypol, binds to Bcl-2 family proteins and induces apoptosis in vitro. Although transsphenoidal surgical excision of the pituitary corticotroph adenoma is the gold standard of care, it is not successful all the time. Medical therapy for Cushing's disease still remains a challenge for the clinicians. We aimed to investigate the cytotoxic and apoptotic effects of AT-101 in mouse pituitary corticotroph tumor AtT20 cells. Methods Cytotoxic effect of AT-101 was assessed by XTT cell viability assay. Apoptosis was shown by measuring DNA fragmentation and Caspase-3/7 activity. Changes in mRNA expressions of apoptosis-related genes were investigated by qPCR array after treatment with AT-101. ACTH was measured by ACTH-EIA Kit. Results AT-101 induced cytotoxicity and apoptosis in AtT20 cells. mRNA levels of pro-apoptotic genes such as TNFR-SF-10B, Bid, PYCARD, Caspase-8, Caspase-3, and Caspase-7 were induced by 2.0-, 1.5-, 1.7-, 1.5-, 1.6-, and 2-fold, respectively, in AtT20 cells by AT-101 treatment. Moreover, some of the anti-apoptotic genes such as BCL2L10, NAIP1, and PAK-7 were reduced by 2.1-, 2.3-, 4.0-fold, respectively, in AtT20 cells. AT-101 also decreased ACTH secretion significantly. Conclusion AT-101 induces apoptosis in mouse pituitary corticotroph tumor cells.Öğe A DIVERSE INDUCTION OF APOPTOSIS BY TRABECTEDIN IN MCF-7 (HER2-/ER+) AND MDA-MB-453 (HER2+/ER-) BREAST CANCER CELLS(Oxford Univ Press, 2013) Atmaca, H.; Bozkurt, E.; Uzunoglu, S.; Uslu, R.; Karaca, B.Öğe A DIVERSE INDUCTION OF APOPTOSIS BY TRABECTEDIN IN MCF-7 (HER2-/ER+) AND MDA-MB-453 (HER2+/ER-) BREAST CANCER CELLS(Oxford Univ Press, 2013) Atmaca, H.; Bozkurt, E.; Uzunoglu, S.; Uslu, R.; Karaca, B.Öğe Docetaxel/zoledronic acid combination triggers apoptosis synergistically through downregulating antiapoptotic Bcl-2 protein level in hormone-refractory prostate cancer cells(Wiley, 2009) Karabulut, B.; Erten, C.; Gul, M. K.; Cengiz, E.; Karaca, B.; Kucukzeybek, Y.; Gorumlu, G.; Atmaca, H.; Uzunoglu, S.; Sanli, U. A.; Baran, Y.; Uslu, R.Docetaxel, a semi-synthetic taxane analogue, is used effectively in the treatment of metastatic prostate cancer. Zoledronic acid, the most potent member of bisphosphonates, has shown pleiotropic anti-tumoral effects on prostate cancer cells. We have explored the possible additive/synergistic effects and the apoptotic pathways induced by combination treatment of docetaxel and zoledronic acid in hormone and drug refractory, PC-3 and DU-145 prostate cancer cells. Combination of docetaxel and zoledronic acid synergistically inhibits cell growth in PC-3 and DU-145 cells. Moreover, this effect was due to downregulation of antiapoptotic protein Bcl-2 in PC-3 and DU-145 cells. In conclusion, docetaxel/zoledronic acid combination is potentially a novel and effective approach for the treatment of prostate cancer. (C) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.Öğe Enhancement of taxane-induced cytotoxicity and apoptosis by gossypol in human breast cancer cell line MCF-7(Imprimatur Publications, 2009) Karaca, B.; Atmaca, H.; Uzunoglu, S.; Karabulut, B.; Sanli, U. A.; Uslu, R.Purpose: Gossypol is a natural polyphenolic compound extracted from cotton plant (Gossypium species) which has shown potent inhibitory effect on cell growth of many types of cancers. In this study, we aimed to evaluate the interaction of gossypol with some conventional drugs known to be effective in the treatment of breast cancer like taxanes, doxorubicin, gemcitabine, cisplatin and vinorelbine, in MCF-7 breast cancer cells. Materials and methods: The XTT viability assay was used to evaluate the cytotoxicity of various cytotoxic agents alone and in combination with gossypol in MCF-7 breast cancer cells. The combination effect analysis of Chou and Talalay was used to identify the most synergistic drug combinations. The possible synergistic effects of the combination of drugs on apoptosis were also evaluated by using two different apoptosis assays. Results: We identified strong synergistic cytotoxic and apoplotic activity of gossypol with taxanes among all other studied cytotoxic drugs. Conclusion: This study provides proof that gossypol combined with taxanes may have potential as a novel future treatment for breast cancer.Öğe FIBROBLAST GROWTH FACTOR RECEPTOR 2 (FGFR2) POLYMORPHISM STATUS OF TURKISH BREAST CANCER PATIENTS(Oxford Univ Press, 2010) Uslu, R.; Karaca, B.; Atmaca, H.; Kisim, A.; Cakar, B.; Karabulut, B.; Sezgin, C.; Uzunoglu, S.Öğe Novel combination of docetaxel and thymoquinone induces synergistic cytotoxicity and apoptosis in DU-145 human prostate cancer cells by modulating PI3K-AKT pathway(Springer-Verlag Italia Srl, 2015) Dirican, A.; Atmaca, H.; Bozkurt, E.; Erten, C.; Karaca, B.; Uslu, R.The treatment of castrate-resistant prostate cancer (CRPC) still remains as an important challenge of daily oncology practice. Docetaxel significantly prolongs overall survival in men with CRPC. Thymoquinone (TQ), one of the flavonoid compounds isolated from Nigealla sativa, has been shown to possess cytotoxic activity against a variety of cancer cell lines. The aim of the study was to investigate the possible synergistic cytotoxic/apoptotic effects of a novel combination, docetaxel and TQ in DU-145 hormone- and drug-refractory prostate cancer cells and their effects on PI3K and ERK signaling pathways. We observed that the combination of docetaxel and TQ resulted in a significant synergistic cytotoxicy and apoptosis as compared to any single agent alone, in a dose-dependent manner. It was found that viability of the combination treated cells was not significantly changed in the presence of LY294002 as compared to inhibitor treated cells. However, in the presence of FR180204, viability of combination treated cells was significantly decreased as compared to inhibitor treated cells. In conclusion, cytotoxic effect of the docetaxel and TQ combination is correlated with the block of the PI3K/Akt signaling pathway in DU-145 cells. Therefore, this combination strategy may be an alternative approach for the challenging era of daily oncologic practice. Also, the combination of docetaxel and TQ might allow a reduction in docetaxel doses and diminish adverse effects of docetaxel while maintaining the therapeutic effect in patients with CRPC.Öğe P53 MODULATES TRABECTEDIN MEDIATED CYTOTOXICITY IN GLIOBLASTOMA MULTIFORME CELLS (U-87MG AND T98G)(Oxford Univ Press, 2013) Bozkurt, E.; Atmaca, H.; Uzunoglu, S.; Uslu, R.; Karaca, B.Öğe P53 MODULATES TRABECTEDIN MEDIATED CYTOTOXICITY IN GLIOBLASTOMA MULTIFORME CELLS (U-87MG AND T98G)(Oxford Univ Press, 2013) Bozkurt, E.; Atmaca, H.; Uzunoglu, S.; Uslu, R.; Karaca, B.Öğe Radiosensitization of hormone-refractory prostate cancer cells by gossypol treatment(Zerbinis Medical Publ, 2010) Akagunduz, O.; Karaca, B.; Atmaca, H.; Uzunoglu, S.; Karabulut, B.; Sanli, U. A.; Haydaroglu, A.; Uslu, R.Purpose: Many drugs have been tested to increase the sensitivity of prostate cancer cells to radiotherapy Gossypol, a natural polyphenolic compound extracted from the cotton plant, is one of the agents the efficacy of which has been investigated in the treatment of prostate cancer for this purpose. The main aim of this study was to investigate the best gossypol application with irradiation, when gossypol was applied either sequentially (24 h before and after irradiation) or concurrently in PC-3 hormone-refractory and radioresistant prostate cancer cells. Methods: The XTT viability assay was used to evaluate the cytotoxicity of different concentrations of gossypol in PC-3 cells. Irradiation was applied to PC-3 cells via 6 MV photon linear accelerator and delivered 24 h before, 24 h after radiation or at the same time with gossypol administration. Results: Gossypol caused radiosensitization of PC-3 cells that are known to be radioresistant, with high Bcl-2 levels. Among different applications of gossypol and irradiation (before, after and concurrent) in prostate cancer cells, the best results were observed by the application of gossypol 24 h before irradiation. Conclusion: Our study suggests that gossypol represents a promising novel anticancer treatment for radiosensitization of human hormone-refractory prostate cancer cells.Öğe Salivary inflammatory burden in pre- and postmenopausal women: Associations with body mass index, patient-reported health, serum cytokines, and periodontal parameters(John Wiley and Sons Inc, 2023) Yakar, N.; Bostanci, N.; Özdemir, G.; Atmaca, H.; Türedi, A.; Şahin, Ç.; Köse, T.Background: The decline of estrogen levels during menopause impacts weight, mood, and overall health, both orally and systemically. This study assessed salivary levels of tumor necrosis factor alpha (TNF-?), interleukin-6 (IL-6), IL-10, and IL-7 in postmenopausal (PMW) and regularly menstruating premenopausal (RMPW) women, while considering serum cytokine levels, body mass index (BMI), periodontal health, and self-reported physical and emotional well-being. Methods: In this study, 75 PMW and 71 RMPW were included. Clinical and periodontal parameters were evaluated, and perceived health was assessed with the Women's Health Questionnaire (WHQ). Cytokine levels in both saliva and serum were quantified by enzyme-linked immunosorbent assay (ELISA). Covariate evaluations of salivary cytokines were conducted using hierarchical linear regression modeling. Results: Cytokines were detectable in saliva from 71 PMW and 67 RMPW. In the initial unadjusted model, IL-7, IL-10, and TNF-? exibited significant differences between RMPW and PMW. However, these differences became non-significant (p > 0.05) in the final model after adjusting for age, which implies a negligible effect of the investigated covariates on salivary cytokine levels when age was considered. Lower levels of IL-6 in PMW, which initially showed no significant difference, became borderline (p = 0.054) in the final model after adjusting for age. Conclusions: After adjusting for multiple factors, no significant difference was found in the salivary levels of the investigated cytokines between RMPW and PMW. Factors such as BMI, perceived health, serum cytokine levels, and periodontal parameters seem to minimally influence these levels in PMW. However, age may be a stronger confounding factor. © 2023 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.Öğe SYNERGISTIC CYTOTOXIC AND APOPTOTIC EFFECT BY AT-101 AND CISPLATIN COMBINATION THROUGH DNA METHYLTRANSFERASE AND HISTONE DEACETYLASE ENZYMES IN HUMAN OVARIAN CANCER CELL LINES(Oxford Univ Press, 2010) Karaca, B.; Atmaca, H.; Kisim, A.; Muslu, U.; Karabulut, B.; Sezgin, C.; Uzunoglu, S.; Uslu, R.Öğe Synergistic cytotoxic/apoptotic effects of AT-101, a phytochemical with BIB-mimetic property, in combination with paclitaxel in human breast cancer cells(Amer Soc Clinical Oncology, 2010) Karaca, S. B.; Muslu, U.; Cakar, B.; Kisim, A.; Atmaca, H.; Purcu, D. Unuvar; Uzunoglu, S.; Uslu, R.Öğe Targeting apoptosis in the hormone- and drug-resistant prostate cancer cell line, DU-145, by gossypol/zoledronic acid combination(Wiley, 2009) Sanli, U. A.; Gorumlu, G.; Erten, C.; Gul, M. K.; Cengiz, E.; Kucukzeybek, Y.; Karaca, B.; Atmaca, H.; Uzunoglu, S.; Karabulut, B.; Uslu, R.Possible synergistic cytotoxic and apoptotic effects of gossypol with zoledronic acid on DU-145 cells were explored, along with the rationale behind any observed synergism due to the different apoptotic proteins involved. XTT cell proliferation assay was used to assess the cytotoxicity, and DNA fragmentation and caspase 3/7 activity were measured to verify apoptosis. Human Apoptosis Array was used to evaluate apoptotic proteins. The synergistic cytotoxic combination treatment had a versatile effect on apoptotic proteins, through inhibition of anti-apoptotic proteins (including cIAP-1, cIAP-2, survivin, livin, claspin, p53, p21, PON-2 and heat shock proteins) and concurrently the induction of pro-apoptotic proteins (Bad, Bax, Fas, FADD, cleaved caspase-3 and p27). Both drugs had a minimal toxicity profile comparing to cytotoxic agents. Combination treatments targeting many pivotal apoptosis-related proteins may be a rationale option for treatment of prostate cancer. (C) 2009 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.Öğe Targeting apoptosis in the hormone- and drug-resistant prostate cancer cell line, DU-145, by gossypol/zoledronic acid combination(Wiley, 2009) Sanli, U. A.; Gorumlu, G.; Erten, C.; Gul, M. K.; Cengiz, E.; Kucukzeybek, Y.; Karaca, B.; Atmaca, H.; Uzunoglu, S.; Karabulut, B.; Uslu, R.Possible synergistic cytotoxic and apoptotic effects of gossypol with zoledronic acid on DU-145 cells were explored, along with the rationale behind any observed synergism due to the different apoptotic proteins involved. XTT cell proliferation assay was used to assess the cytotoxicity, and DNA fragmentation and caspase 3/7 activity were measured to verify apoptosis. Human Apoptosis Array was used to evaluate apoptotic proteins. The synergistic cytotoxic combination treatment had a versatile effect on apoptotic proteins, through inhibition of anti-apoptotic proteins (including cIAP-1, cIAP-2, survivin, livin, claspin, p53, p21, PON-2 and heat shock proteins) and concurrently the induction of pro-apoptotic proteins (Bad, Bax, Fas, FADD, cleaved caspase-3 and p27). Both drugs had a minimal toxicity profile comparing to cytotoxic agents. Combination treatments targeting many pivotal apoptosis-related proteins may be a rationale option for treatment of prostate cancer. (C) 2009 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.
