Please use this identifier to cite or link to this item: http://hdl.handle.net/11452/30033
Title: Enhanced cytotoxic activity of doxorubicin through the inhibition of autophagy in triple negative breast cancer cell line
Authors: Ulukaya, Engin
Uludağ Üniversitesi/Fen Edebiyet Fakültesi/Biyoloji Bölümü.
0000-0001-5238-2432
0000-0002-3127-742X
0000-0003-2647-5875
0000-0002-6729-7908
Aydınlık, Seyma
Erkısa, Merve
Cevatemre, Buse
Sarımahmut, Mehmet
Dere, Egemen
Arı, Ferda
ABI-2909-2020
AAM-1001-2020
AHD-2050-2022
AAG-8288-2021
AAH-5068-2021
AAG-7012-2021
57190280044
57126208900
55693788600
44661687400
6603627015
24376085300
Keywords: Biochemistry & molecular biology
Biophysics
Autophagy
Breast cancer
Drug resistance
Necroptosis
Synergism
Double-edged-sword
Induced apoptosis
Protective autophagy
Death
activation
Induction
Cycle
Hydroxychloroquine
Macroautophagy
Tumorigenesis
Issue Date: 10-Nov-2016
Publisher: Elsevier
Citation: Aydınlık, S. vd. (2017). ''Enhanced cytotoxic activity of doxorubicin through the inhibition of autophagy in triple negative breast cancer cell line''. Biochimica et Biophysica Acta - General Subjects, 186(2), 49-57.
Abstract: Background: 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.
URI: https://doi.org/10.1016/j.bbagen.2016.11.013
https://www.sciencedirect.com/science/article/pii/S0304416516304160
1872-8006
http://hdl.handle.net/11452/30033
ISSN: 0304-4165
Appears in Collections:Scopus
Web of Science

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.