The Antitumor Didox Acts as an Iron Chelator in Hepatocellular Carcinoma Cells.
RRM2
antitumor compound
didox
iron chelators
iron metabolism
Journal
Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453
Informations de publication
Date de publication:
02 Sep 2019
02 Sep 2019
Historique:
received:
18
07
2019
revised:
28
08
2019
accepted:
29
08
2019
entrez:
5
9
2019
pubmed:
5
9
2019
medline:
5
9
2019
Statut:
epublish
Résumé
Ribonucleotide reductase (RR) is the rate-limiting enzyme that controls the deoxynucleotide triphosphate synthesis and it is an important target of cancer treatment, since it is expressed in tumor cells in proportion to their proliferation rate, their invasiveness and poor prognosis. Didox, a derivative of hydroxyurea (HU), is one of the most potent pharmaceutical inhibitors of this enzyme, with low in vivo side effects. It inhibits the activity of the subunit RRM2 and deoxyribonucleotides (dNTPs) synthesis, and it seems to show iron-chelating activity. In the present work, we mainly investigated the iron-chelating properties of didox using the HA22T/VGH cell line, as a model of hepatocellular carcinoma (HCC). We confirmed that didox induced cell death and that this effect was suppressed by iron supplementation. Interestingly, cell treatments with didox caused changes of cellular iron content, TfR1 and ferritin levels comparable to those caused by the iron chelators, deferoxamine (DFO) and deferiprone (DFP). Chemical studies showed that didox has an affinity binding to Fe
Identifiants
pubmed: 31480699
pii: ph12030129
doi: 10.3390/ph12030129
pmc: PMC6789654
pii:
doi:
Types de publication
Journal Article
Langues
eng
Références
Cancer Res. 1987 Apr 1;47(7):1749-50
pubmed: 3815370
Annu Rev Biochem. 1988;57:349-74
pubmed: 3052277
Oncotarget. 2015 Aug 7;6(22):18748-79
pubmed: 26125440
J Med Chem. 1979 May;22(5):589-92
pubmed: 458812
Exp Hematol. 2001 May;29(5):623-32
pubmed: 11376876
Blood. 1995 Dec 1;86(11):4295-306
pubmed: 7492790
Prog Biophys Mol Biol. 2001 Nov;77(3):177-268
pubmed: 11796141
Exp Cell Res. 1985 Dec;161(2):277-84
pubmed: 2998833
Cancer Res. 2003 Oct 15;63(20):6583-94
pubmed: 14583450
Cancer Res. 1979 Mar;39(3):844-51
pubmed: 427774
Cancer Biol Ther. 2002 Sep-Oct;1(5):539-45
pubmed: 12496485
Br J Cancer. 1990 Mar;61(3):447-50
pubmed: 2183873
Inorg Chem. 2012 Apr 16;51(8):4473-81
pubmed: 22468647
Int J Mol Sci. 2017 Aug 07;18(8):null
pubmed: 28783123
Mol Cancer Ther. 2015 Nov;14(11):2411-21
pubmed: 26333382
Nat Rev Cancer. 2013 May;13(5):342-55
pubmed: 23594855
Crit Rev Clin Lab Sci. 1997;34(6):503-28
pubmed: 9439883
Semin Oncol. 1992 Jun;19(3 Suppl 9):1-10
pubmed: 1641648
Life Sci. 1997;61(22):2231-7
pubmed: 9393942
Trends Biochem Sci. 2016 Mar;41(3):274-286
pubmed: 26725301
PLoS One. 2014 Nov 17;9(11):e112619
pubmed: 25402485
Oncotarget. 2016 Jan 12;7(2):1984-99
pubmed: 26675256
Future Med Chem. 2009 Dec;1(9):1643-70
pubmed: 21425984
Br J Haematol. 2006 Oct;135(1):52-61
pubmed: 16925573
Br J Cancer. 1988 Jul;58(1):70-2
pubmed: 3048353
Blood. 1990 May 15;75(10):1903-19
pubmed: 2186818
FEMS Microbiol Rev. 2003 Jun;27(2-3):215-37
pubmed: 12829269
Eur J Pharmacol. 2013 Oct 15;718(1-3):361-9
pubmed: 24021537
Life Sci. 1981 Mar 2;28(9):1007-14
pubmed: 7012518
J Biol Chem. 1995 Oct 13;270(41):24209-15
pubmed: 7592626
Lung Cancer. 2005 Feb;47(2):183-92
pubmed: 15639717
Anticancer Res. 2011 Oct;31(10):3475-81
pubmed: 21965764
J Infect Dis. 2017 Oct 17;216(7):907-918
pubmed: 28973651
J Biol Chem. 1970 Oct 25;245(20):5228-33
pubmed: 4319235
Blood. 1997 Apr 15;89(8):3025-38
pubmed: 9108424
Pharmacol Ther. 1985;29(2):239-54
pubmed: 3939037
World J Gastroenterol. 2015 Jul 28;21(28):8478-91
pubmed: 26229392