Scopus
Permanent URI for this collectionhttps://hdl.handle.net/11452/20668
Browse
Browsing by Author "0000-0001-5238-2432"
Now showing 1 - 7 of 7
- Results Per Page
- Sort Options
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 Enhanced cytotoxic activity of doxorubicin through the inhibition of autophagy in triple negative breast cancer cell line(Elsevier, 2016-11-10) Ulukaya, Engin; Aydınlık, Seyma; Erkısa, Merve; Cevatemre, Buse; Sarımahmut, Mehmet; Dere, Egemen; Arı, Ferda; Uludağ Üniversitesi/Fen Edebiyet Fakültesi/Biyoloji Bölümü.; 0000-0001-5238-2432; 0000-0002-3127-742X; 0000-0003-2647-5875; 0000-0002-6729-7908; ABI-2909-2020; AAM-1001-2020; AHD-2050-2022; AAG-8288-2021; AAH-5068-2021; AAG-7012-2021; 57190280044; 57126208900; 55693788600; 44661687400; 6603627015; 24376085300Background: The outcome of triple negative breast cancer is still poor and requires improvement with better therapy options. Autophagy has recently been shown to play a role in anticancer drug resistance. Therefore, we investigated if the effectiveness of doxorubicin was augmented by the inhibition of autophagy. Methods: MDA-MB-231 was used as a model cell line for triple negative breast cancer and 3-methyladenine was used as an inhibitor of autophagy. Cells were treated with 0.46-1.84 mu M doxorubicin and 2.5-10 mu M 3-methyladenine for 48 h. Cell death mode was examined with M30 and M65 ELISA assays. ROS level and LDH activity was examined and the cellular acidic compartment of cells was monitored by acridine orange staining. The expression of various autophagy and apoptosis related proteins/genes were evaluated with Western blotting and RT-qPCR respectively. Results: Synergism was observed between the compounds (CI value < 1.0). RT-qPCR analysis revealed that the combination resulted in a down-regulation of autophagy-related genes. Moreover, the combination resulted in a different cell death modality, upregulating necroptosis-related genes. This suggests that the mode of cell death may switch from apoptosis to necroptosis, which is a more severe form of cell death, when autophagy is inhibited. These results were further confirmed at protein level by Western blotting. Conclusion: Inhibition of autophagy seems to sensitize triple negative breast cancer cells to doxorubicin, warranting further in vivo studies for the proof of this concept. General significance: Autophagy has a key role in drug resistance in MDA-MB-231 cells. Therefore combinatorial approaches may effectively overcome resistance.Item Induction of autophagy enhances apoptotic cell death via epidermal growth factor receptor inhibition by canertinib in cervical cancer cells(Elsevier, 2019-05) Ulukaya, Engin; Aydınlık, Şeyma; Dere, Egemen; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0001-5238-2432; 0000-0001-9572-1051; AAH-5068-2021; ABI-2909-2020; 57190280044; 6603627015Background: It has been known epidermal growth factor receptor (EGFR) frequently overexpressed in cervical cancer. High levels of EGFR expression in their tumors leads to a poor prognosis and inhibition frequently induces autophagy in cancer cells. This study aimed to investigate whether EGFR inhibition by canertinib induces autophagy and this induction influence the effect of Palladium (Pd) (II) complex and 5-fluorouracil (5-FU) especially in nontoxic doses. Methods: Cytotoxicity was evaluated by using SRB assay. Apoptosis, autophagy, and EGFR key markers were determined by flow cytometry, fluorescence staining, and immunoblotting. Colony formation, invasion, and wound healing assays were performed to investigate cell proliferation, invasion, and migration, respectively. Results: Blocking EGFR by the pan-ErbB tyrosine kinase inhibitor canertinib inhibited cell growth of HeLa cervical cancer cells in combination with Pd(II) complex and 5-FU. Combination of canertinib and Pd(II) complex promotes autophagy and apoptosis of HeLa cancer cells via blockade of the PI3K/AKT and MAPK/ERK pathway, which leads to cervical cancer cell death. ROS accumulation and DNA damage were increased after combinatorial treatment which causes depolarization of the mitochondrial inner membrane and leads to apoptotic cell death. Canertinib combined with Pd(II) complex leads to inhibition of migration and invasion. Conclusion: Inhibition of EGFR signaling by canertinib in combination with Pd(II) complex promotes apoptosis and autophagy via blockade of the PI3K/AKT and MAPK/ERK. General significance: The cytotoxic activity of Pd(II) complex and 5-FU on HeLa cells is mediated by EGFR inhibition and autophagy induction, leading to activation of mitochondrial apoptotic cell death.Item A promising therapeutic combination for metastatic prostate cancer: Chloroquine as autophagy inhibitor and palladium(II) barbiturate complex(Elsevier, 2020-08) Akar, Remzi Okan; Aztopal, Nazlıhan; Cevatemre, Buse; Erkısa, Merve; Aydınlık, Şeyma; Cevatemre, Buse; Çelikler, Serap; Yılmaz, Veysel Turan; Arı, Ferda; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; 0000-0002-3127-742X; 0000-0001-5238-2432; 0000-0002-4177-3478; 0000-0002-2849-3332; 0000-0002-6729-7908; AAM-1001-2020; ABI-2909-2020; AAH-2767-2021; L-7238-2018; AAG-7012-2021; 57126208900; 57190280044; 8234554800; 56441123900; 24376085300Autophagy is a catabolic process for cells that can provide energy sources and allows cancer cells to evade cell death. Therefore, studies on the combination of autophagy inhibitors with drugs are increasing as a new treatment modality in cancer. Previously, we reported the anti-tumor activity of a Palladium (Pd)(II) complex against different types of cancer in vitro and in vivo. Chloroquine (CQ), the worldwide used anti-malarial drug, has recently been focused as a chemosensitizer in cancer treatment. The aim of this study was to investigate the efficacy of a combined treatment of these agents that work through different mechanisms to provide an effective treatment modality for metastatic prostate cancer that is certainly fatal. Metastatic prostate cancer cell lines (PC-3 and LNCaP) were treated with Pd (II) complex, CQ, and their combination. The combination enhanced apoptosis by increasing phosphatidylserine translocation and pro-apoptotic proteins. Apoptosis was confirmed by the use of apoptosis inhibitor. The formation of acidic vesicular organelles (AVOs) was observed by acridine orange staining in fluorescence microscopy. The Pd (II) complex increased AVOs formation in prostate cancer cells and CQ-pretreatment has potentiated this effect. Importantly, treatment with CQ suppressed the pro-survival function of autophagy, which might have contributed to enhanced cytotoxicity. In addition, PI3K/AKT/mTOR-related protein expressions were altered after the combination of treatments. Our results suggest that combination treatment enhances apoptotic cell death possibly via the inhibition of autophagy, and may therefore be regarded as a novel and better approach for the treatment of metastatic prostate cancer.Item Structures and biochemical evaluation of silver(I) 5,5-diethylbarbiturate complexes with bis(diphenylphosphino)alkanes as potential antimicrobial and anticancer agents(Elsevier, 2017-08-28) Aygün, Muhittin; Yılmaz, Veysel T.; İçsel, Ceyda; Batur, Jenaidullah; Aydınlık, Şeyma; Şahintürk, Pınar; Uludağ Üniversitesi/Fen-Edebiyet Fakültesi/Kimya Bölümü.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Veteriner Fakültesi/Farmakoloji ve Toksikoloji Anabilim Dalı.; 0000-0002-2849-3332; 0000-0002-2717-2430; 0000-0001-5238-2432; L-7238-2018; AAI-3342-2021; AHD-1718-2022; ABI-2909-2020; 56441123900; 55551960400; 57194706926; 57190280044; 55342852700New silver(I) 5,5-diethylbarbiturate (barb) complexes with a series of bis(diphenylphosphino)alkanes such as 1,1-bis(diphenylphosphino)methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis-(diphenylphosphino)propane (dppp) and 1,4-bis(diphenylphosphino)butane (dppb) were synthesized and characterized. [Ag-2(barb)(2)(mu-dppm)(2) (1), [Ag-2(barb)(2)(mu-dppe)(DMSO)(2)] (2) and [Ag-2(barb)(2)( dppp)2](3) were binuclear, while [Ag(barb)(mu-dppb)] (4) was a coordination polymer. 1-4 effectively bind to the G/C rich region of the major groove of DNA and interact with BSA via hydrophobic interactions in accordance with molecular docking studies. All complexes displayed significant DNA cleavage in the presence of H2O2. 1-4 exhibited more specificity against Gram-positive bacteria than Gram-negative bacteria, but 2 targets both bacterial strains, being comparable to AgNO3 and silver sulfadiazine. Complex 1 has a strong growth inhibitory effect on A549 cells, while 2 and 3 exhibit considerable cytotoxicity against MCF-7 cells. The complexes showed high accumulation in the cytosol fraction of the cells. Mechanistic studies showed that 1 and 2 display effective cell growth inhibition by triggering S and G2/M phase arrest, induce apoptosis via mitochondrial pathways and also damage to DNA due to the overproduction of ROS.Item Synergistic interactions between resveratrol and doxorubicin inhibit angiogenesis both in vitro and in vivo(Polska Akademia Nauk, 2020) Üvez, Ayça; Esener, Osman Behzat Burak; Erkısa, Merve; Karakuş, Dilek; Armutak, Elif İlkay; Aydınlık, Şeyma; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0001-5238-2432; ABI-2909-2020; 57190280044Resveratrol is a polyphenolic compound which is found in many nutrients including grapes, peanuts, raspberries, and apples. Anti-proliferative, anti-angiogenic and apoptotic effects of resveratrol have been shown on various cancer cells. Doxorubicin is considered as one of the most effective anticancer agents and reveals its antitumor activity by induction of apoptosis and inhibition of angiogenesis. Our study reports for the first time the potent ability of resveratrol in combination with doxorubicin to inhibit angiogenesis in vitro and in vivo. The cytotoxic effect of resveratrol (1.56-100 mu M), doxorubicin (0.01-0.92 mu M) and their combination were analyzed in the human umbilical vein endothelial cells (HUVECs) by ATP assay. In vitro angiogenesis was evaluated using tube formation assay in HUVECs. In vivo anti-angiogenic activity was assessed in a chick chorioallantoic membrane (CAM) model using fertilized chicken eggs. All test groups were compared to thalidomide as a positive control, three concentrations of resveratrol (10-5-2.5 mu g/pellet) and a 2 mu g/pellet concentration of doxorubicin was examined. All data were evaluated statistically. Resveratrol and doxorubicin alone displayed inhibitory effects on angiogenesis and cell viability at higher doses. However, the combination of resveratrol and doxorubicin exhibited a significant dose-dependent inhibition of CAM angiogenesis in vivo as well as proliferation and tube formation in HUVECs compared to the positive control (+/-)-thalidomide. Our results suggest that resveratrol in combination with doxorubicin is a novel strategy in the prevention and treatment of angiogenesis.Item Synthesis, structures and biomolecular interactions of new silver(I) 5,5-diethylbarbiturate complexes of monophosphines targeting Gram-positive bacteria and breast cancer cells(Royal Soc Chemistry, 2017-05-24) Büyükgüngör, Orhan; Yılmaz, Veysel T.; İçsel, Ceyda; Batur, Jenaidullah; Aydınlık, Seyma; Cengiz, Murat; Uludağ Üniversitesi/Fen-Edebiyet Fakültesi/Kimya Bölümü.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Veteriner Fakültesi/Farmakoloji ve Toksikoloji Anabilim Dalı.; 0000-0002-2849-3332; 0000-0002-2717-2430; 0000-0001-5238-2432; L-7238-2018; AAI-3342-2021; ABI-2909-2020; ABE-5935-2020; 56441123900; 55551960400; 57194706926; 57190280044; 16635026700A series of new silver(I) 5,5-diethylbarbiturate (barb) complexes with the formulas [Ag-2(mu-barb)(2)(PPh3)(2)] (1), [Ag(barb)(PPh2Cy)] (2), [Ag(barb)(PPhCy2)] (3) and [Ag(barb)(PCy3)] (4) (PPh3 = triphenylphosphine, PPh2Cy = diphenylcyclohexylphosphine, PPhCy2 = dicyclohexylphenylphosphine and PCy3 = tricyclo-hexylphosphine) were synthesized and fully characterized by elemental analysis, IR, NMR, ESI-MS and X-ray crystallography. All the complexes display a significant affinity towards DNA with a groove binding mode and also strongly bind to BSA via hydrophobic interactions. Lipophilicity increases from 1 to 4 with an increasing number of Cy groups in the phosphine ligands. Screening of the in vitro antimicrobial activity of 1-4 against the strains of Gram-negative (S. typhimurium ATCC 14028, E. coli ATCC 25922 and O157:H7) and Gram-positive (L. garvieae 40456, S. aureus ATCC 25923, and ATCC 33591) bacteria demonstrated that all the complexes exhibit very high activity and specific selectivity against the Gram-positive bacteria, compared to AgNO3 and silver sulfadiazine. Furthermore, the growth inhibitory effects of 1-4 on four human cancer cell lines (MCF-7, PC-3, A549 and HT-29) showed that 4 has a potent cytotoxic activity against MCF-7 cells, significantly higher than cisplatin and carboplatin. The effects of the complexes on the inhibition of the cells are closely related to their lipophilicity as well as DNA/protein binding. The induction of apoptosis of MCF-7 cells treated with 4 was probed through Hoechst 33342 staining, Annexin V positivity and caspase 3/7 activity. In addition, increased ROS levels in the presence of 4 are most likely responsible for damage to both mitochondria and genomic DNA.