Titanium Tackles the Endoplasmic Reticulum: A First Genomic Study on a Titanium Anticancer Metallodrug.
Biochemistry
Cancer
Genomics
Organometallic Chemistry
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
24 Jul 2020
24 Jul 2020
Historique:
received:
16
02
2020
revised:
07
05
2020
accepted:
05
06
2020
pubmed:
26
6
2020
medline:
26
6
2020
entrez:
26
6
2020
Statut:
ppublish
Résumé
PhenolaTi is an advanced non-toxic anticancer chemotherapy; this inert bis(phenolato)bis(alkoxo) Ti(IV) complex demonstrates the intriguing combination of high and wide efficacy with no detected toxicity in animals. Here we unravel the cellular pathways involved in its mechanism of action by a first genome study on Ti(IV)-treated cells, using an attuned RNA sequencing-based available technology. First, phenolaTi induced apoptosis and cell-cycle arrest at the G2/M phase in MCF7 cells. Second, the transcriptome of the treated cells was analyzed, identifying alterations in pathways relating to protein translation, DNA damage, and mitochondrial eruption. Unlike for common metallodrugs, electrophoresis assay showed no inhibition of DNA polymerase activity. Reduced in vitro cytotoxicity with added endoplasmic reticulum (ER) stress inhibitor supported the ER as a putative cellular target. Altogether, this paper reveals a distinct ER-related mechanism by the Ti(IV) anticancer coordination complex, paving the way for wider applicability of related techniques in mechanistic analyses of metallodrugs.
Identifiants
pubmed: 32585595
pii: S2589-0042(20)30448-X
doi: 10.1016/j.isci.2020.101262
pmc: PMC7322074
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
101262Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests. Relating patent: Tshuva EY and Hochman J; Cytotoxic titanium and vanadium complexes PCT/IL2013/05,069 filled 15/08/2013.
Références
ChemMedChem. 2014 Jun;9(6):1294-8
pubmed: 24677761
Int J Mol Med. 2017 Aug;40(2):271-280
pubmed: 28656226
Anticancer Res. 2015 Jun;35(6):3147-54
pubmed: 26026074
Drug Metab Dispos. 2016 Dec;44(12):1859-1866
pubmed: 27233287
ChemMedChem. 2012 Apr;7(4):703-8
pubmed: 22262543
Metallomics. 2018 Aug 15;10(8):1053-1064
pubmed: 29989630
Tumour Biol. 2014 Jun;35(6):5431-9
pubmed: 24535777
Chemistry. 2016 Jul 11;22(29):9986-95
pubmed: 27320784
J Am Chem Soc. 2014 Oct 15;136(41):14413-6
pubmed: 25247635
Science. 2005 Feb 11;307(5711):935-9
pubmed: 15705855
Met Ions Life Sci. 2018 Feb 5;18:
pubmed: 29394020
Sci Rep. 2018 Jun 26;8(1):9705
pubmed: 29946136
Clin Cancer Res. 2002 Nov;8(11):3311-4
pubmed: 12429616
J Am Chem Soc. 2011 Oct 26;133(42):16812-4
pubmed: 21967133
Br J Cancer. 2010 Jan 19;102(2):428-35
pubmed: 20087356
Stress. 2009 Nov;12(6):499-506
pubmed: 19212922
Chem Commun (Camb). 2013 May 25;49(42):4785-7
pubmed: 23598498
Cancer Biol Ther. 2006 Jul;5(7):723-8
pubmed: 16861899
Metallomics. 2015 Oct;7(10):1439-50
pubmed: 26338673
PLoS One. 2011 Mar 21;6(3):e17869
pubmed: 21445304
Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):5016-21
pubmed: 22411801
Arch Pharm (Weinheim). 2007 Mar;340(3):117-26
pubmed: 17315259
J Med Chem. 2015 Nov 12;58(21):8475-90
pubmed: 26488797
Cell Cycle. 2009 Dec;8(23):3838-47
pubmed: 19887912
Dalton Trans. 2015 Feb 7;44(5):2497
pubmed: 25526919
Inorg Chem. 2012 Feb 6;51(3):1796-804
pubmed: 22220885
Metallomics. 2017 Apr 19;9(4):346-356
pubmed: 28164202
Chemistry. 2010 Mar 1;16(9):2775-89
pubmed: 20104550
Molecules. 2015 Oct 09;20(10):18526-38
pubmed: 26473816
Nat Cell Biol. 2013 May;15(5):481-90
pubmed: 23624402
Chem Soc Rev. 2017 Feb 20;46(4):1040-1051
pubmed: 28124046
J Inorg Biochem. 2016 Oct;163:250-257
pubmed: 27090292
Cancer Res. 2005 Dec 15;65(24):11597-604
pubmed: 16357170
Angew Chem Int Ed Engl. 1979 Jun;18(6):477-8
pubmed: 111586
Front Oncol. 2017 Apr 26;7:78
pubmed: 28491820
Front Pharmacol. 2017 Jan 31;8:5
pubmed: 28197098
Metallomics. 2016 Feb;8(2):236-51
pubmed: 26612010
J Biol Inorg Chem. 2007 Aug;12(6):825-30
pubmed: 17483967
J Clin Oncol. 1997 Jan;15(1):389-400
pubmed: 8996166
OMICS. 2016 Mar;20(3):139-51
pubmed: 26983021
Crit Rev Oncol Hematol. 1993 Feb;14(1):77-87
pubmed: 8103989
J Am Chem Soc. 2013 Sep 25;135(38):14060-3
pubmed: 24041161
Immunol Rev. 2000 Aug;176:19-29
pubmed: 11043765
Pharmacol Ther. 1999 Sep;83(3):181-215
pubmed: 10576292
Inorg Chem. 2014 Mar 17;53(6):3170-6
pubmed: 24588655
J Biol Chem. 2014 Feb 7;289(6):3352-64
pubmed: 24347168
Curr Top Med Chem. 2012;12(3):219-35
pubmed: 22236158
Met Ions Biol Syst. 2004;42:353-84
pubmed: 15206108
Chem Commun (Camb). 2012 Jun 11;48(46):5790-2
pubmed: 22549385
Radiother Oncol. 2005 Aug;76(2):168-76
pubmed: 16026872
Chemistry. 2009;15(10):2403-15
pubmed: 19156656
RSC Adv. 2018 Feb 5;8(11):5822-5827
pubmed: 30009018
Mol Cell. 2010 May 28;38(4):576-89
pubmed: 20513432
Cell Death Dis. 2016 Jun 02;7(6):e2247
pubmed: 27253411
J Vis Exp. 2013 Nov 10;(81):e50767
pubmed: 24300943
Mol Cell Biol. 2004 Oct;24(19):8504-18
pubmed: 15367671
J Inorg Biochem. 2016 Oct;163:362-373
pubmed: 27118029
Dalton Trans. 2018 Mar 12;47(11):3669-3673
pubmed: 29451281
Nat Rev Drug Discov. 2005 Apr;4(4):307-20
pubmed: 15789122
Chem Rev. 1999 Sep 8;99(9):2467-98
pubmed: 11749487
Inorg Chem. 2011 Feb 7;50(3):1030-8
pubmed: 21214265
Biomark Insights. 2016 Aug 24;11:113-21
pubmed: 27594783
ChemMedChem. 2018 Nov 6;13(21):2290-2296
pubmed: 30203598
Br J Cancer. 1998 Jun;77(12):2088-97
pubmed: 9649119
Dalton Trans. 2007 Aug 28;(32):3474-82
pubmed: 17680034
Mol Cell Biol. 2009 Mar;29(6):1649-60
pubmed: 19114550
Chem Soc Rev. 2018 Feb 5;47(3):909-928
pubmed: 29170783
Chem Rev. 2014 Apr 23;114(8):4540-63
pubmed: 24456146
Genome Biol. 2016 Apr 28;17:77
pubmed: 27121950
Cancer Res. 2008 Jan 15;68(2):605-14
pubmed: 18199558
J Cell Biochem. 2018 Dec;119(12):9707-9719
pubmed: 30129075
Curr Drug Metab. 2004 Jun;5(3):211-24
pubmed: 15180491
Mol Cell Biol. 2014 Aug;34(16):3041-52
pubmed: 24912683
Crit Rev Oncol Hematol. 2002 Jun;42(3):309-15
pubmed: 12050022
Angew Chem Int Ed Engl. 2012 Oct 15;51(42):10515-7
pubmed: 22961758