Fatty Acid Synthase Inhibitor G28 Shows Anticancer Activity in EGFR Tyrosine Kinase Inhibitor Resistant Lung Adenocarcinoma Models.
EGCG
EGFR TKI
FASN inhibitors
NSCLC
STAT3
resistance
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
19 May 2020
19 May 2020
Historique:
received:
26
03
2020
revised:
29
04
2020
accepted:
16
05
2020
entrez:
23
5
2020
pubmed:
23
5
2020
medline:
23
5
2020
Statut:
epublish
Résumé
Epidermal growth factor receptor (EGFR) tyrosine kinases inhibitors (TKIs) are effective therapies for non-small cell lung cancer (NSCLC) patients whose tumors harbor an EGFR activating mutation. However, this treatment is not curative due to primary and secondary resistance such as T790M mutation in exon 20. Recently, activation of transducer and activator of transcription 3 (STAT3) in NSCLC appeared as an alternative resistance mechanism allowing cancer cells to elude the EGFR signaling. Overexpression of fatty acid synthase (FASN), a multifunctional enzyme essential for endogenous lipogenesis, has been related to resistance and the regulation of the EGFR/Jak2/STAT signaling pathways. Using EGFR mutated (EGFRm) NSCLC sensitive and EGFR TKIs' resistant models (Gefitinib Resistant, GR) we studied the role of the natural polyphenolic anti-FASN compound (-)-epigallocatechin-3-gallate (EGCG), and its derivative G28 to overcome EGFR TKIs' resistance. We show that G28's cytotoxicity is independent of TKIs' resistance mechanisms displaying synergistic effects in combination with gefitinib and osimertinib in the resistant T790M negative (T790M-) model and showing a reduction of activated EGFR and STAT3 in T790M positive (T790M+) models. Our results provide the bases for further investigation of G28 in combination with TKIs to overcome the EGFR TKI resistance in NSCLC.
Identifiants
pubmed: 32438613
pii: cancers12051283
doi: 10.3390/cancers12051283
pmc: PMC7281741
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Agència de Gestió d'Ajuts Universitaris i de Recerca
ID : 2017SGR00385
Références
Cancer Lett. 2007 Jun 28;251(2):199-210
pubmed: 17129668
Future Oncol. 2010 Apr;6(4):551-62
pubmed: 20373869
PLoS One. 2015 Jun 24;10(6):e0131241
pubmed: 26107737
Int J Mol Sci. 2020 Mar 03;21(5):
pubmed: 32138321
N Engl J Med. 2004 May 20;350(21):2129-39
pubmed: 15118073
Adv Biol Regul. 2014 Jan;54:214-21
pubmed: 24080588
Mol Cancer Ther. 2013 May;12(5):589-97
pubmed: 23443806
Curr Drug Targets. 2017;18(2):147-159
pubmed: 26758667
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Oncol Rep. 2014 Mar;31(3):1343-9
pubmed: 24366444
Ann N Y Acad Sci. 2009 Aug;1171:59-76
pubmed: 19723038
BMC Cancer. 2012 Jul 06;12:280
pubmed: 22769244
Expert Opin Ther Pat. 2016 Aug;26(8):907-16
pubmed: 27338088
Cancer Res. 2013 May 15;73(10):3051-61
pubmed: 23542356
Lancet. 2016 Apr 2;387(10026):1354-1356
pubmed: 26777918
Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):E2127-33
pubmed: 22773810
Oncotarget. 2017 Jul 18;8(29):47305-47316
pubmed: 28521301
Urology. 2012 Aug;80(2):484.e9-15
pubmed: 22554590
Life Sci. 2014 Apr 1;100(2):110-7
pubmed: 24530290
Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8695-9
pubmed: 7567999
J Lipid Res. 2013 Mar;54(3):776-85
pubmed: 23319743
Cell Prolif. 2008 Feb;41(1):59-85
pubmed: 18211286
J Agric Food Chem. 2012 Mar 14;60(10):2480-9
pubmed: 22313388
Aging (Albany NY). 2011 Mar;3(3):192-222
pubmed: 21422497
Nat Rev Mol Cell Biol. 2002 Sep;3(9):651-62
pubmed: 12209125
Int J Biochem Mol Biol. 2010 Jul 18;1(1):69-89
pubmed: 20706604
Adv Enzyme Regul. 1984;22:27-55
pubmed: 6382953
Nat Commun. 2017 Sep 4;8(1):410
pubmed: 28871105
Lipids Health Dis. 2019 May 24;18(1):118
pubmed: 31122252
Cell Death Dis. 2014 Nov 06;5:e1509
pubmed: 25375374
Clin Cancer Res. 2004 Feb 15;10(4):1212-8
pubmed: 14977817
Oncol Lett. 2018 Apr;15(4):4578-4584
pubmed: 29541228
Cancer Res. 2006 Jun 15;66(12):5977-80
pubmed: 16778164
Front Oncol. 2017 May 31;7:113
pubmed: 28620581
Mol Cell Endocrinol. 2017 Aug 15;451:15-23
pubmed: 28088467
Cancer Res. 2008 Jul 15;68(14):5524-8
pubmed: 18632602
Biochem Biophys Res Commun. 2001 Nov 16;288(5):1200-6
pubmed: 11700039
Clin Cancer Res. 2007 Oct 1;13(19):5665-9
pubmed: 17908954
Curr Genomics. 2017 Apr;18(2):106-131
pubmed: 28367072
EMBO Mol Med. 2018 Mar;10(3):
pubmed: 29449326
PLoS One. 2012;7(2):e31067
pubmed: 22348037
Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20932-7
pubmed: 18093943
Nutrients. 2017 Nov 10;9(11):
pubmed: 29125563
Molecules. 2019 Mar 15;24(6):
pubmed: 30875891
J Biomed Res. 2013 May;27(3):220-30
pubmed: 23720678
Clin Cancer Res. 2016 Sep 15;22(18):4687-97
pubmed: 27106068
Target Oncol. 2018 Apr;13(2):141-156
pubmed: 29423594
Oncotarget. 2016 Aug 9;7(32):51251-51269
pubmed: 27323414
Cancers (Basel). 2018 Jul 27;10(8):
pubmed: 30060526
Molecules. 2018 May 11;23(5):
pubmed: 29751678
Mol Cancer. 2019 Nov 4;18(1):153
pubmed: 31684958
Eur J Surg Oncol. 2014 Mar;40(3):311-7
pubmed: 24332948
Clin Cancer Res. 2013 Jan 1;19(1):279-90
pubmed: 23091115
Breast Cancer Res Treat. 2008 Jun;109(3):471-9
pubmed: 17902053
Int J Biochem Mol Biol. 2011 Jan 1;2(1):89-98
pubmed: 21331354
Mol Cancer Ther. 2008 Feb;7(2):263-70
pubmed: 18281512
Cancer Discov. 2012 Oct;2(10):922-33
pubmed: 22956644
Cancer Chemother Pharmacol. 2015 May;75(5):917-22
pubmed: 25735252
Sci Rep. 2020 Feb 12;10(1):2444
pubmed: 32051483
J Natl Cancer Inst. 2017 Sep 1;109(9):
pubmed: 28376152
Cancer Cell. 2014 Aug 11;26(2):207-21
pubmed: 25065853