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Browsing by Author "0000-0001-5238-2432"
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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.