Please use this identifier to cite or link to this item: http://hdl.handle.net/11452/34509
Title: Induction of autophagy enhances apoptotic cell death via epidermal growth factor receptor inhibition by canertinib in cervical cancer cells
Authors: Ulukaya, Engin
Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.
0000-0001-5238-2432
0000-0001-9572-1051
Aydınlık, Şeyma
Dere, Egemen
AAH-5068-2021
ABI-2909-2020
57190280044
6603627015
Keywords: Autophagy
Apoptosis
Tyrosine kinase inhibitors
Epidermal growth factor receptor
Mitochondrial depolarization
Phase-II trial
Palladium(II) saccharinate complex
Tyrosine kinase inhibitors
Pan-erbb inhibitor
In-vitro
Egf receptor
Cytotoxic activity
Plus cetuximab
Carcinoma
CI-1033
Biochemistry & molecular biology
Biophysics
Issue Date: May-2019
Publisher: Elsevier
Citation: Aydınlık, Ş. vd. (2019). "Induction of autophagy enhances apoptotic cell death via epidermal growth factor receptor inhibition by canertinib in cervical cancer cells". Biochimica et Biophysica Acta - General Subjects, 1863(5), 903-916.
Abstract: Background: 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.
URI: https://doi.org/10.1016/j.bbagen.2019.02.014
https://www.sciencedirect.com/science/article/pii/S0304416519300480
http://hdl.handle.net/11452/34509
ISSN: 0304-4165
1872-8006
Appears in Collections:PubMed
Scopus
Web of Science

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