Comparison of autophagy inducibility in various tyrosine kinase inhibitors and their enhanced cytotoxicity via inhibition of autophagy in cancer cells in combined treatment with azithromycin.
Autophagy
Cancer
Macrolide antibiotics
Tyrosine kinase inhibitor
azithromycin, AZM
bafilomycin A1, BAF
dasatinib, DAS
gefitinib, GEF
imatinib, IMA
lapatinib, LAP
lenvatinib, LEN
osimertinib, OSI
receptor tyrosine kinase, RTK
sorafenib, SOR
tivantinib, TIV
tyrosine kinase inhibitors, TKIs
Journal
Biochemistry and biophysics reports
ISSN: 2405-5808
Titre abrégé: Biochem Biophys Rep
Pays: Netherlands
ID NLM: 101660999
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
21
11
2019
revised:
27
01
2020
accepted:
21
02
2020
entrez:
21
3
2020
pubmed:
21
3
2020
medline:
21
3
2020
Statut:
epublish
Résumé
Tyrosine kinase inhibitors (TKIs) induce autophagy in many types of cancer cells. We previously reported that gefitinib (GEF) and imatinib (IMA) induce autophagy in epidermal growth factor receptor (EGFR) knock-out A549 and non-BCR-ABL-expressing leukemia cell lines, respectively. This evidence suggests that TKI-induced autophagy is independent of the original target molecules. The present study compared the autophagy-inducing abilities of various TKIs, regardless of their targets, by quantitative autophagy flux assay. We established stable clones expressing the GFP-LC3-mCherry-LC3ΔG plasmid in A549, PC-9, and CAL 27 cell lines and assessed autophagy inducibility by monitoring the fluorescent ratios of GFP-LC3 to mCherry-LC3ΔG using an IncuCyte live cell imaging system during exposure to TKIs viz; GEF, osimertinib (OSI), lapatinib (LAP), lenvatinib (LEN), sorafenib (SOR), IMA, dasatinib (DAS), and tivantinib (TIV). Among these TKIs, DAS, GEF, and SOR exhibited prominent autophagy induction in A549 and PC-9 cells. In CAL 27 cells, IMA, SOR, and LEN, but not GEF, TIV, or OSI, exhibited autophagy induction. In the presence of azithromycin (AZM), which showed an inhibitory effect on autophagy flux, TKIs with prominent autophagy inducibility exhibited enhanced cytotoxicity
Identifiants
pubmed: 32195376
doi: 10.1016/j.bbrep.2020.100750
pii: S2405-5808(20)30059-5
pii: 100750
pmc: PMC7078496
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100750Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2020 The Author(s).
Références
Genes Cancer. 2010 Jan;1(1):40-9
pubmed: 20811583
Nat Commun. 2017 Nov 17;8(1):1580
pubmed: 29146937
PLoS One. 2016 Dec 15;11(12):e0164529
pubmed: 27977675
Autophagy. 2016 Jun 2;12(6):1029-46
pubmed: 27166522
Cell. 2013 Sep 12;154(6):1269-84
pubmed: 24034250
Lung Cancer. 2017 May;107:73-83
pubmed: 27372519
PLoS One. 2011;6(6):e18691
pubmed: 21655094
Mol Cell Biol. 2017 Feb 15;37(5):
pubmed: 27920255
Sci Signal. 2014 Jan 21;7(309):ra9
pubmed: 24448649
Int J Oncol. 2016 Jan;48(1):45-54
pubmed: 26718641
Int J Oncol. 2013 May;42(5):1541-50
pubmed: 23546223
Nat Commun. 2019 Apr 12;10(1):1693
pubmed: 30979895
Nat Rev Cancer. 2012 Apr 26;12(6):401-10
pubmed: 22534666
Mol Cancer. 2019 May 24;18(1):101
pubmed: 31126310
Oncogene. 2010 Feb 25;29(8):1190-202
pubmed: 19935717
Biochem Biophys Res Commun. 2015 May 22;461(1):28-34
pubmed: 25858318
Biochem Biophys Res Commun. 2010 Jan 1;391(1):310-5
pubmed: 19912986
Dev Cell. 2016 May 23;37(4):337-349
pubmed: 27219062
Cell Res. 2014 Feb;24(2):139-40
pubmed: 24418759
Nat Med. 2019 Apr;25(4):620-627
pubmed: 30833748
Proc Natl Acad Sci U S A. 2019 Mar 5;116(10):4508-4517
pubmed: 30709910
Mol Cancer Ther. 2010 Aug;9(8):2220-31
pubmed: 20682655
Mol Cell. 2016 Nov 17;64(4):835-849
pubmed: 27818143
Int J Oncol. 2018 Apr;52(4):1165-1177
pubmed: 29484439
Cell Death Differ. 2018 Mar;25(3):486-541
pubmed: 29362479
Cancers (Basel). 2017 Mar 24;9(4):
pubmed: 28338617