Chloroquine enhances the efficacy of chemotherapy drugs against acute myeloid leukemia by inactivating the autophagy pathway.
acute myeloid leukemia
autophagy
chloroquine phosphate
cytarabine
daunorubicin
drug resistant
idarubicin
multi-omics
Journal
Acta pharmacologica Sinica
ISSN: 1745-7254
Titre abrégé: Acta Pharmacol Sin
Pays: United States
ID NLM: 100956087
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
19
01
2023
accepted:
16
05
2023
pmc-release:
01
11
2024
medline:
2
11
2023
pubmed:
15
6
2023
entrez:
14
6
2023
Statut:
ppublish
Résumé
Current therapy for acute myeloid leukemia (AML) is largely hindered by the development of drug resistance of commonly used chemotherapy drugs, including cytarabine, daunorubicin, and idarubicin. In this study, we investigated the molecular mechanisms underlying the chemotherapy drug resistance and potential strategy to improve the efficacy of these drugs against AML. By analyzing data from ex vivo drug-response and multi-omics profiling public data for AML, we identified autophagy activation as a potential target in chemotherapy-resistant patients. In THP-1 and MV-4-11 cell lines, knockdown of autophagy-regulated genes ATG5 or MAP1LC3B significantly enhanced AML cell sensitivity to the chemotherapy drugs cytarabine, daunorubicin, and idarubicin. In silico screening, we found that chloroquine phosphate mimicked autophagy inactivation. We showed that chloroquine phosphate dose-dependently down-regulated the autophagy pathway in MV-4-11 cells. Furthermore, chloroquine phosphate exerted a synergistic antitumor effect with the chemotherapy drugs in vitro and in vivo. These results highlight autophagy activation as a drug resistance mechanism and the combination therapy of chloroquine phosphate and chemotherapy drugs can enhance anti-AML efficacy.
Identifiants
pubmed: 37316630
doi: 10.1038/s41401-023-01112-8
pii: 10.1038/s41401-023-01112-8
pmc: PMC10618541
doi:
Substances chimiques
Idarubicin
ZRP63D75JW
Daunorubicin
ZS7284E0ZP
Cytarabine
04079A1RDZ
Chloroquine
886U3H6UFF
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2296-2306Informations de copyright
© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.
Références
Ann Intern Med. 2006 Mar 7;144(5):337-43
pubmed: 16520474
Mol Med Rep. 2018 May;17(5):6859-6865
pubmed: 29512762
Nucleic Acids Res. 2023 Jan 6;51(D1):D638-D646
pubmed: 36370105
Onco Targets Ther. 2019 Mar 11;12:1937-1945
pubmed: 30881045
J Cell Sci. 2012 May 15;125(Pt 10):2349-58
pubmed: 22641689
Haematologica. 2009 Jan;94(1):10-6
pubmed: 19118375
Oxid Med Cell Longev. 2020 Jul 24;2020:2524174
pubmed: 32774666
Blood. 2002 Feb 15;99(4):1373-80
pubmed: 11830489
Nature. 2019 May;569(7757):503-508
pubmed: 31068700
Bioinformatics. 2011 Feb 1;27(3):431-2
pubmed: 21149340
Cancers (Basel). 2018 Nov 09;10(11):
pubmed: 30423907
Science. 2010 Dec 3;330(6009):1344-8
pubmed: 21127245
BMC Syst Biol. 2014;8 Suppl 4:S11
pubmed: 25521941
Clin Cancer Res. 2011 Feb 15;17(4):654-66
pubmed: 21325294
Nature. 2007 Aug 9;448(7154):645-6
pubmed: 17687303
Carcinogenesis. 2015 Nov;36(11):1263-74
pubmed: 26354777
Pharmacogenomics J. 2015 Apr;15(2):109-18
pubmed: 25558979
Cancer Discov. 2022 Feb;12(2):388-401
pubmed: 34789538
Cureus. 2022 Dec 31;14(12):e33165
pubmed: 36726936
J Clin Med. 2020 Jun 17;9(6):
pubmed: 32560371
Front Pharmacol. 2013 Aug 01;4:89
pubmed: 23914174
J Biol Chem. 2004 Apr 30;279(18):18641-7
pubmed: 14988409
Int J Biochem Cell Biol. 2019 Jun;111:63-71
pubmed: 30710750
Cancer Cell. 2006 Jul;10(1):51-64
pubmed: 16843265
Nat Rev Mol Cell Biol. 2008 Jul;9(7):517-31
pubmed: 18568040
Kaohsiung J Med Sci. 2017 May;33(5):215-223
pubmed: 28433067
Cell. 2017 Nov 30;171(6):1437-1452.e17
pubmed: 29195078
Genes Dev. 2011 Mar 1;25(5):460-70
pubmed: 21317241
Mol Med Rep. 2015 Jan;11(1):91-8
pubmed: 25322694
J Biol Chem. 2014 Jun 13;289(24):17163-73
pubmed: 24794870
Int J Mol Sci. 2020 Nov 26;21(23):
pubmed: 33256191
J Clin Invest. 2015 Jan;125(1):42-6
pubmed: 25654549
Cancer Cell. 2012 Apr 17;21(4):532-46
pubmed: 22516261
Autophagy. 2014;10(12):2122-42
pubmed: 25427136
J Exp Clin Cancer Res. 2018 Aug 28;37(1):201
pubmed: 30153855
Nat Commun. 2017 Nov 22;8(1):1679
pubmed: 29162833
Mol Cell Oncol. 2014 Jul 15;1(1):e29911
pubmed: 27308318
Mol Cell Biol. 2001 Jul;21(13):4129-39
pubmed: 11390642
Oncotarget. 2014 Dec 15;5(23):11886-96
pubmed: 25361010
EMBO J. 2010 Jun 2;29(11):1792-802
pubmed: 20418806
N Engl J Med. 2015 Sep 17;373(12):1136-52
pubmed: 26376137
Nucleic Acids Res. 2013 Jan;41(Database issue):D955-61
pubmed: 23180760
Cancer Res. 2008 Apr 1;68(7):2349-57
pubmed: 18381442
J Biol Regul Homeost Agents. ;31(3):645-652
pubmed: 28954454
Eur J Haematol. 2002 Sep;69(3):171-8
pubmed: 12406011
Cell Cycle. 2005 Jan;4(1):131-9
pubmed: 15539958
Expert Opin Ther Pat. 2015;25(9):1003-24
pubmed: 26013494
Blood. 2005 Jul 1;106(1):318-27
pubmed: 15784732
Cancer Cell Int. 2019 Jul 29;19:199
pubmed: 31384174
Blood. 2017 Jan 26;129(4):424-447
pubmed: 27895058
JOP. 2014 Mar 10;15(2):189-97
pubmed: 24618445
Curr Clin Pharmacol. 2015;10(1):73-81
pubmed: 24219000
Cell Death Dis. 2017 Jan 12;8(1):e2540
pubmed: 28079894
Prostate. 2019 Jan;79(1):44-53
pubmed: 30178500
Cell. 2018 Apr 19;173(3):649-664.e20
pubmed: 29677511
Mol Aspects Med. 1995;16(1):1-78
pubmed: 7783568
J Cell Biol. 2001 Feb 19;152(4):657-68
pubmed: 11266458
Science. 2006 Sep 29;313(5795):1929-35
pubmed: 17008526
Cancer Lett. 2015 Mar 1;358(1):17-26
pubmed: 25524555
Clin Cancer Res. 2009 Sep 1;15(17):5308-16
pubmed: 19706824