Browsing by Author "Dimas, Konstantinos"
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Item Anti-angiogenic effect of a palladium(II)-saccharinate complex of terpyridine in vitro and in vivo(Elsevier, 2016-09-05) İlkay, Elif Armutak; Gürel, Ebru Gürevin; Kıyan, Hülya Tuba; Dimas, Konstantinos; Aydınlık, Şeyma; Yilmaz, Veysel Turan; Ulukaya, Engin; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Moleküler Biyoloji Bölümü.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Klinik Biyokimya Anabilim Dalı.; 0000-0002-2849-3332; 0000-0002-2849-3332; ABI-2909-2020; L-7238-2018; K-5792-2018; 57190280044; 7006269202; 6602927353Anti-angiogenic activity of palladium (Pd) (II)-based complexes is unknown despite their quite powerful anticancer activity. This study was therefore carried out to evaluate both in vivo anti-angiogenic effect and in vitro cytotoxic activity of a Pd(II)-based complex. ([Pd(sac)(terpy)](sac).4H(2)O(sac = saccharinate and terpy = 2,2':6',2 ''-terpyridine)) on HUVEC cells. The anti-angiogenic activity of the complex was evaluated in vivo using the chick embryo chorioallantoic membrane (CAM) assay, tube formation assay and the cytotoxicity was screened using the MIT viability assays. The CAM treated with the complex (50 mu g/pellet) showed a strikingly high anti-angiogenic effect (score 1.1 +/- 0.2) compared to the positive controls cortisone, prednisone and (+/-)-thalidomide (e.g. (+/-)-thalidomide score 0.9 +/- 0.2) tested at the same concentration. Furthermore, the complex showed neither membrane toxicity nor irritation at the tested concentration. According to the MTT assays, the human umbilical vein endothelial cell (HUVEC) viability was inhibited in a dose-dependent manner at tested concentrations (1.56-100 mu M). Pd(II) complex also reduced the tube network at the lower dose than the compared with thalidomide. These results suggest that the Pd(II)-complex has strong anti-angiogenic activity, which adds an important feature to the previously-described anticancer activity of the complex.Item Anti-cancer activity of a novel palladium(II) complex on human breast cancer cells in vitro and in vivo(Elsevier, 2011-10) Dimas, Konstantinos; İkitimur, Elif İlkay; Ulukaya, Engin; Arı, Ferda; Yılmaz, Veysel T.; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; 0000-0002-6729-7908; 0000-0002-2849-3332; K-5792-2018; AAG-7012-2021; L-7238-2018; 6602927353; 24376085300; 7006269202Anti-cancer effects of a newly-synthesized palladium(II) complex, [Pd(sac)(terpy)](sac)center dot 4H(2)O (sac = saccharinate, and terpy = 2,2':6',2 ''-terpyridine), were tested against human breast cancer cell lines, MCF-7 and MDA-MB-231. The Pd complex had a strong anti-growth effect in a dose- and time-dependent manner in vitro. This effect was also confirmed by the experiment performed on Balb/c mice in vivo. The IC50 values were 0.09 mu M for MDA-MB-231 and 3.05 mu M for MCF-7. It was also very effective in disrupting the formation of MDA-MB-231 tubules on matrigel, indicative of a putative anti-invasive activity. It induced apoptosis via the cell death genes of DR4 and DR5. In conclusion, this newly-synthesized Pd (II) complex represents a potentially active novel drug for the breast cancer treatment.Item Cell death-inducing effect of novel palladium(II) and platinum(II) complexes on non-small cell lung cancer cells in vitro(Springer, 2011-10) Dimas, Konstantinos; Sakellaridis, Nikos; Ulukaya, Engin; Arı, Ferda; Sarımahmut, Mehmet; Güney, Emel; Yılmaz, Veysel T.; Uludağ Üniversitesi/Tıp Fakültesi/Klinik Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Fen-Edebiyat/Kimya Anabilim Dalı.; Uludağ Üniversitesi/Fen-Edebiyat/Biyoloji Anabilim Dalı.; 0000-0002-6729-7908; 0000-0003-2647-5875; AAG-7012-2021; K-5792-2018; AAG-8288-2021; 6602927353; 24376085300; 44661687400; 25027291500; 7006269202Purpose Treatment for lung cancer is still far from satisfying rates. Therefore, there is a need for novel anticancer agents. For this purpose, novel platinum and palladium complexes {[Pd(sac)(terpy)](sac).4H(2)O (Complex 1), [Pt(sac)(terpy)] (sac).5H(2)O (Complex 2), [PdCl(terpy)](sac).2H(2)O (Complex 3), [PtCl(terpy)](sac).2H(2)O (Complex 4)} have been tested against three different non-small cell lung cancer cell lines (A549, H1299, PC-3). Methods Growth-inhibiting effcts have been tested by the MTT and ATP viability assays. Apoptosis has been detected by the caspase-cleaved cytokeratin 18 (M30-antigen) assay. Necrosis has been detected by staining the cells with fluorescent dyes. Mitotic index has been calculated by counting the mitotic figures after staining with hematoxylin. Results The complex 3 exhibited significant anti-growth effects, and its anti-growth effect was more powerful than that of cisplatin that is a standard chemotherapeutic agent for this type of cancer. The complexes did not induce apoptosis, while necrosis clearly took place. Conclusions Novel Pd(II) complex ([PdCl(terpy)] (sac).2H(2)O) seems to represent a potentially active drug against non-small cell lung cancer cell lines, and further studies in vivo are warranted.Item Chloroquine used in combination with chemotherapy synergistically suppresses growth and angiogenesis in vitro and in vivo(Int Inst Anticancer Research, 2018-05-21) Gürel, Ebru Gürevin; Kıyan, Hülya Tuba; Esener, Osman Behzat Burak; Üvez, Ayca; Ulukaya, Engin; Dimas, Konstantinos; Armutak, Elif İlkay; Aydınlık, Şeyma; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0001-5238-2432; ABI-2909-2020; 57190280044Background: The inhibition of autophagy using pharmacological inhibitors such as chloroquine may be an effective strategy to overcome chemotherapy or resistance to anti-angiogenic therapy. Materials and Methods: The cytotoxic effect of doxorubicin (0.1-1 mu M), chloroquine (0.25-32 ,mu M) and their combination were investigated by employing ATP assay in human umbilical vein endothelial cells (HUVECs). The effect of doxorubicin and chloroquine combination was also measured using tube formation assay on Matrigel. The anti-angiogenic activities of doxorubicin (2.5 mu g/pellet) and chloroquine (15 mu g/pellet), their combination, and standards (50 mu g/pellet) were tested in vivo using the chick embryo chorioallantoic membrane (CAM) assay. Results: The combination of doxorubicin and chloroquine significantly had a stronger anti-angiogenic effect than the positive control (+/-)-thalidomide and doxorubicin alone in the CAM assay and in vitro tube-formation assay. Conclusion: Chloroquine enhanced the anti-angiogenic effect of doxorubicin on CAM at the tested concentrations.Item Promising anti-cancer activity of a novel palladium (II) complex on human breast cancer cells in vitro and in vivo(Elsevier, 2011-09) Dimas, Konstantinos; Armutak, Elif; Vournas, Costas; Ulukaya, Engin; Arı, Ferda; Güney, E.; Yılmaz, Veysel T.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0002-2849-3332; 0000-0002-6729-7908; K-5792-2018; AAG-7012-2021; L-7238-2018Item A promising natural product, pristimerin, results in cytotoxicity against breast cancer stem cells in vitro and xenografts in vivo through apoptosis and an incomplete autopaghy in breast cancer(Academic Press, 2017-12-02) Tsimplouli, Chrisiida; Sereti, Evangelia; Dimas, Konstantinos; Ilkay Armutak, Elif; Gurevin, Ebru Gurel; Üvez, Ayça; Mori, Mattia; Berardozzi, Simone; Ingallina, Cinzia; D'Acquarica, Ilaria; Botta, Bruno; Özpolat, Bülent; Ulukaya, Engin; Cevatemre, Buse; Erkısa, Merve; Aztopal, Nazlıhan; Karakaş, Didem; Alper, Pınar; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0002-3127-742X; 0000-0003-3118-8061; 0000-0002-3781-6834; 0000-0001-9631-3551; AHD-2050-2022; AAM-1001-2020; L-6687-2018; L-6682-2018; 55693788600; 57126208900; 55853882900; 56422040600; 57197858774Several natural products have been suggested as effective agents for the treatment of cancer. Given the important role of CSCs (Cancer Stem Cells) in cancer, which is a trendy hypothesis, it is worth investigating the effects of pristimerin on CSCs as well as on the other malignant cells (MCF-7 and MDA-MB-231) of breast cancer. The anti-growth activity of pristimerin against MCF-7 and MCF-7s (cancer stem cell enriched population) cells was investigated by real time viability monitorization (xCELLigence System (R)) and ATP assay, respectively. Mode of cell death was evaluated using electron and fluorescence microscopies, western blotting (autophagy, apoptosis and ER-stress related markers) and flow cytometry (annexin-V staining, caspase 3/7 activity, BCL-2 and PI3K expressions). Pristimerin showed an anti-growth effect on cancer cells and cancer stem cells with IC50 values ranging at 0.38-1.75 mu M. It inhibited sphere formation at relatively lower doses (<1.56 mu M). Apoptosis was induced in MCF-7 and MCF-7s cells. In addition, extensive cytoplasmic vacuolation was observed, implying an incompleted autophagy as evidenced by the increase of autophagy-related proteins (p62 and LC3-II) with an unfolded protein response (UPR). Pristimerin inhibited the growth of MCF-7 and MDA-MB-231-originated xenografts in NOD.CB17-Prkdc(scid)/J mice. In mice, apoptosis was further confirmed by cleavage of PARP, activation of caspase 3 and/or 7 and TUNEL staining. Taken together, pristimerin shows cytotoxic activity on breast cancer both in vitro and in vivo. It seems to represent a robust promising agent for the treatment of breast cancer. Pristimerin's itself or synthetic novel derivatives should be taken into consideration for novel potent anticancer agent(s).