Riluzole regulates pancreatic cancer cell metabolism by suppressing the Wnt-β-catenin pathway.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
30 06 2022
30 06 2022
Historique:
received:
08
12
2021
accepted:
03
05
2022
entrez:
30
6
2022
pubmed:
1
7
2022
medline:
6
7
2022
Statut:
epublish
Résumé
Most cancer cells rely on aerobic glycolysis to support uncontrolled proliferation and evade apoptosis. However, pancreatic cancer cells switch to glutamine metabolism to survive under hypoxic conditions. Activation of the Wnt/β-catenin pathway induces aerobic glycolysis by activating enzymes required for glucose metabolism and regulating the expression of glutamate transporter and glutamine synthetase. The results demonstrate that riluzole inhibits pancreatic cancer cell growth and has no effect on human pancreatic normal ductal epithelial cells. RNA-seq experiments identified the involvement of Wnt and metabolic pathways by riluzole. Inhibition of Wnt-β-catenin/TCF-LEF pathway by riluzole suppresses the expression of PDK, MCT1, cMyc, AXIN, and CyclinD1. Riluzole inhibits glucose transporter 2 expression, glucose uptake, lactate dehydrogenase A expression, and NAD + level. Furthermore, riluzole inhibits glutamate release and glutathione levels, and elevates reactive oxygen species. Riluzole disrupts mitochondrial homeostasis by inhibiting Bcl-2 and upregulating Bax expression, resulting in a drop of mitochondrial membrane potential. Finally, riluzole inhibits pancreatic cancer growth in KPC (Pdx1-Cre, LSL-Trp53
Identifiants
pubmed: 35773307
doi: 10.1038/s41598-022-13472-y
pii: 10.1038/s41598-022-13472-y
pmc: PMC9246955
doi:
Substances chimiques
CTNNB1 protein, mouse
0
beta Catenin
0
Glutamine
0RH81L854J
Riluzole
7LJ087RS6F
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
11062Informations de copyright
© 2022. The Author(s).
Références
J Neuroinflammation. 2016 Sep 10;13(1):242
pubmed: 27612942
Cancer Cell. 2005 May;7(5):469-83
pubmed: 15894267
Ecotoxicol Environ Saf. 1996 Feb;33(1):38-43
pubmed: 8744922
J Clin Psychopharmacol. 2017 Jun;37(3):355-358
pubmed: 28338546
Cell Cycle. 2006 Jan;5(1):7-10
pubmed: 16322692
J Carcinog. 2011 Mar 17;10:5
pubmed: 21483657
J Clin Psychiatry. 2009;70 Suppl 2:32-8
pubmed: 19371505
PLoS One. 2011 Jan 31;6(1):e16530
pubmed: 21304978
Science. 1998 Aug 28;281(5381):1322-6
pubmed: 9735050
Clin Cancer Res. 2011 Nov 15;17(22):7080-92
pubmed: 21844014
Cell Rep. 2019 May 21;27(8):2281-2291.e5
pubmed: 31116975
Cancer Cell. 2010 Sep 14;18(3):207-19
pubmed: 20832749
PLoS One. 2011;6(9):e25166
pubmed: 21980390
Oncotarget. 2015 Oct 13;6(31):31151-63
pubmed: 26439804
Cell. 2008 Sep 5;134(5):703-7
pubmed: 18775299
Cell Rep. 2019 Aug 20;28(8):1949-1960.e6
pubmed: 31433973
Early Interv Psychiatry. 2008 Aug;2(3):136-46
pubmed: 19649153
Nat Rev Cancer. 2002 Dec;2(12):897-909
pubmed: 12459728
Semin Cancer Biol. 2009 Feb;19(1):4-11
pubmed: 19101633
Arch Environ Contam Toxicol. 1996 Oct;31(3):368-77
pubmed: 8854830
Br J Pharmacol. 2014 Mar;171(5):1195-209
pubmed: 24032637
Clin Cancer Res. 2012 Nov 1;18(21):5888-901
pubmed: 23072969
Mol Syst Biol. 2011 Aug 16;7:523
pubmed: 21847114
Oncologist. 2008 May;13(5):562-76
pubmed: 18515741
Cancer Lett. 2016 Nov 28;382(2):157-165
pubmed: 27612558
Cancer Cell. 2015 Feb 9;27(2):257-70
pubmed: 25670081
Braz J Med Biol Res. 1999 Sep;32(9):1053-61
pubmed: 10464379
CNS Spectr. 2005 Oct;10(10):808-19
pubmed: 16400244
Neuropsychiatr Dis Treat. 2013;9:1101-12
pubmed: 23976856
Neuropharmacology. 2017 Mar 15;115:193-202
pubmed: 26896755
BMC Cancer. 2013 Apr 17;13:194
pubmed: 23590467
Cancer Treat Rev. 2007 May;33(3):289-98
pubmed: 17343986
Neuro Oncol. 2013 Jun;15(6):691-706
pubmed: 23482671
Muscle Nerve. 2000 Feb;23(2):294-5
pubmed: 10639627
Best Pract Res Clin Gastroenterol. 2002 Jun;16(3):435-55
pubmed: 12079268
Cell Mol Life Sci. 2015 May;72(10):1881-92
pubmed: 25609364
J Cell Biochem. 2019 Nov 11;:
pubmed: 31709624
Cancer Lett. 2003 May 8;194(1):13-9
pubmed: 12706854
Cancer Res. 2006 Sep 15;66(18):8927-30
pubmed: 16982728
Pharmacol Ther. 1992;53(1):31-65
pubmed: 1641401
Immunol Res. 2010 Mar;46(1-3):155-64
pubmed: 19763894
Oncotarget. 2017 Jul 4;8(27):44639-44653
pubmed: 28591718
Mol Brain. 2018 Jan 4;11(1):1
pubmed: 29301575
Trends Biochem Sci. 2010 Aug;35(8):427-33
pubmed: 20570523
Breast Cancer Res Treat. 2015 May;151(1):57-73
pubmed: 25859923
Cell Cycle. 2009 Dec;8(23):3984-4001
pubmed: 19923890
Oncotarget. 2014 Mar 15;5(5):1363-81
pubmed: 24658058
Genes (Basel). 2019 Nov 11;10(11):
pubmed: 31718047
PLoS One. 2013 May 27;8(5):e64588
pubmed: 23724064
Oncol Lett. 2019 Mar;17(3):2695-2702
pubmed: 30854043
Breast Cancer Res Treat. 2016 Jun;157(2):217-228
pubmed: 27146584
Int J Dev Neurosci. 2013 Nov;31(7):482-6
pubmed: 23777615
Exp Cell Res. 2000 Apr 10;256(1):50-7
pubmed: 10739651
Lancet. 2011 Aug 13;378(9791):607-20
pubmed: 21620466
Int J Cancer. 2011 Nov 15;129(10):2349-59
pubmed: 21207374
Oncotarget. 2017 May 20;8(57):96697-96709
pubmed: 29228563
Nature. 2013 Apr 4;496(7443):101-5
pubmed: 23535601
Stem Cell Res. 2017 Mar;19:139-147
pubmed: 28167342
Cancer Res. 2007 Mar 1;67(5):2298-305
pubmed: 17332361
Mutagenesis. 1994 Nov;9(6):505-15
pubmed: 7854141
Curr Opin Cell Biol. 2002 Dec;14(6):715-20
pubmed: 12473344
Cancer Chemother Pharmacol. 2007 Mar;59(4):447-54
pubmed: 16855842
JAMA. 2007 Jan 17;297(3):267-77
pubmed: 17227978
Cell. 2012 Apr 27;149(3):656-70
pubmed: 22541435
Bioorg Med Chem. 2012 Sep 15;20(18):5642-8
pubmed: 22892214
J UOEH. 2016 Mar 1;38(1):1-8
pubmed: 26972939
Int J Mol Sci. 2013 Aug 12;14(8):16600-16
pubmed: 23941782
Cell Rep. 2019 Oct 29;29(5):1287-1298.e6
pubmed: 31665640
J Mol Neurosci. 2017 Aug;62(3-4):368-379
pubmed: 28689265
Nanomedicine. 2015 Nov;11(8):2061-70
pubmed: 26199979
Science. 1956 Feb 24;123(3191):309-14
pubmed: 13298683
J Cell Mol Med. 2019 Dec;23(12):7999-8009
pubmed: 31602781
J Nutr. 2001 Sep;131(9 Suppl):2539S-42S; discussion 2550S-1S
pubmed: 11533309