Dendrogenin A synergizes with Cytarabine to Kill Acute Myeloid Leukemia Cells In Vitro and In Vivo.
Acute myeloid leukemia
Dendrogenin A
cholesterol metabolism
primary cancer cells
synergy
tumor suppressor
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
29 Jun 2020
29 Jun 2020
Historique:
received:
21
05
2020
revised:
19
06
2020
accepted:
25
06
2020
entrez:
3
7
2020
pubmed:
3
7
2020
medline:
3
7
2020
Statut:
epublish
Résumé
Dendrogenin A (DDA) is a mammalian cholesterol metabolite that displays potent antitumor properties on acute myeloid leukemia (AML). DDA triggers lethal autophagy in cancer cells through a biased activation of the oxysterol receptor LXRβ, and the inhibition of a sterol isomerase. We hypothesize that DDA could potentiate the activity of an anticancer drug acting through a different molecular mechanism, and conducted in vitro and in vivo combination tests on AML cell lines and patient primary tumors. We report here results from tests combining DDA with antimetabolite cytarabine (Ara-C), one of the main drugs used for AML treatment worldwide. We demonstrated that DDA potentiated and sensitized AML cells, including primary patient samples, to Ara-C in vitro and in vivo. Mechanistic studies revealed that this sensitization was LXRβ-dependent and was due to the activation of lethal autophagy. This study demonstrates a positive in vitro and in vivo interaction between DDA and Ara-C, and supports the clinical evaluation of DDA in combination with Ara-C for the treatment of AML.
Identifiants
pubmed: 32610562
pii: cancers12071725
doi: 10.3390/cancers12071725
pmc: PMC7407291
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Agence Nationale de la Recherche
ID : ANR-11-RPIB-015-02
Organisme : Agence Nationale de la Recherche
ID : ANR-11-PHUC-0001
Organisme : Agence Nationale de la Recherche
ID : ANR-10-LABX-57
Déclaration de conflit d'intérêts
A.R. is employed by the company Dendrogenix. The remaining authors declare no competing financial interests. C.R: Consultancy within the past two years: Jazz Pharma, Daiichi-Sankyo, Astellas, Novartis; Research funding: Amgen, Novartis, Celgene, Jazz Pharma, Agios, Daiichi-Sankyo, Astellas, Sunesis, Roche, MaatPharma, Honoraria: Abbvie, Janssen, Jazz Pharma, Daiichi-Sankyo, Astellas, Novartis, Celgene, Roche, Otsuka, Macrogenics, Pfizer.
Références
J Lipid Res. 2011 Jan;52(1):6-34
pubmed: 20929975
Leukemia. 1997 Dec;11(12):2079-86
pubmed: 9447824
Autophagy. 2008 Oct;4(7):911-3
pubmed: 18690009
J Biol Chem. 2008 Aug 8;283(32):21847-52
pubmed: 18544538
Crit Rev Oncol Hematol. 2017 Feb;110:20-34
pubmed: 28109402
Biochem Pharmacol. 2018 Jul;153:75-81
pubmed: 29409832
Nat Commun. 2017 Dec 4;8(1):1903
pubmed: 29199269
Autophagy. 2018;14(3):555-557
pubmed: 29368971
Nat Biotechnol. 2012 Jul 10;30(7):679-92
pubmed: 22781697
Nat Rev Cancer. 2015 Apr;15(4):216-24
pubmed: 25786697
Blood. 2005 Aug 15;106(4):1154-63
pubmed: 15870183
Proc Natl Acad Sci U S A. 1974 Oct;71(10):4229-31
pubmed: 4530299
Front Oncol. 2015 Dec 14;5:280
pubmed: 26697412
Biochem Pharmacol. 2018 Jan;147:170-182
pubmed: 29203368
Curr Opin Pharmacol. 2012 Dec;12(6):696-703
pubmed: 22917620
Can J Biochem Physiol. 1959 Aug;37(8):911-7
pubmed: 13671378
Blood. 2017 Feb 2;129(5):547-552
pubmed: 27956388
Science. 2014 Mar 28;343(6178):1445-6
pubmed: 24675946
J Steroid Biochem Mol Biol. 2019 Sep;192:105390
pubmed: 31170473
Curr Med Chem. 2015;22(30):3533-49
pubmed: 26179999
Cancer Res. 1990 Feb 1;50(3):552-7
pubmed: 2153442
Prostaglandins Leukot Essent Fatty Acids. 2015 Mar;94:49-54
pubmed: 25481335
Blood. 2018 Mar 8;131(10):1081-1093
pubmed: 29343483
Nat Med. 2007 Jun;13(6):730-5
pubmed: 17515897
Blood. 2003 May 1;101(9):3628-34
pubmed: 12506040
Int Rev Cell Mol Biol. 2016;321:29-88
pubmed: 26811286
Biochem Pharmacol. 2017 Nov 15;144:18-28
pubmed: 28642035
Autophagy. 2016;12(1):1-222
pubmed: 26799652
Cancer Res. 1992 Jul 15;52(14):3886-91
pubmed: 1377599
Nat Rev Cancer. 2017 Sep;17(9):528-542
pubmed: 28751651
Subcell Biochem. 2008;49:567-88
pubmed: 18751927
Biochem Biophys Res Commun. 2014 Apr 11;446(3):681-6
pubmed: 24406163
Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):14-20
pubmed: 25696830
Res Lett Biochem. 2008;2008:801849
pubmed: 22820672
Int J Cell Biol. 2012;2012:931956
pubmed: 22291708
Blood. 2016 Sep 22;128(12):1614-24
pubmed: 27480114
Nat Rev Drug Discov. 2017 Jul;16(7):487-511
pubmed: 28529316
Nat Commun. 2013;4:1840
pubmed: 23673625
J Med Chem. 2009 Dec 10;52(23):7765-77
pubmed: 19821610
Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13520-5
pubmed: 20615952
Leukemia. 2014 Apr;28(4):749-60
pubmed: 23823656
J Steroid Biochem Mol Biol. 2019 Nov;194:105447
pubmed: 31415823
Blood. 2004 Sep 15;104(6):1816-24
pubmed: 15161671
Cancer Res. 2018 Sep 1;78(17):4803-4808
pubmed: 30120211
Cell Metab. 2015 Apr 7;21(4):517-26
pubmed: 25863245