Heme-Dependent ER Stress Apoptosis: A Mechanism for the Selective Toxicity of the Dihydroartemisinin, NSC735847, in Colorectal Cancer Cells.
FOLFOX
artemisinin
colorectal cancer
endoplasmic reticulum stress
heme
iron
reactive oxygen species
selective toxicity
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2020
2020
Historique:
received:
17
12
2019
accepted:
15
05
2020
entrez:
7
7
2020
pubmed:
7
7
2020
medline:
7
7
2020
Statut:
epublish
Résumé
Colorectal cancer (CRC) is a leading cause of cancer death in the United States. Artemisinin derivatives, including the dihydroartemisinin (DHA) monomers, are widely used as clinical agents for the treatment of malaria. Numerous studies demonstrate that these molecules also display antineoplastic activity with minimal toxicity. Of interest, dimeric DHA molecules are more active than their monomeric counterparts. Our previous data showed that the DHA dimer, NSC735847, was a potent inducer of death in different cancer cell types. However, the mechanism of action and activity of NSC735847 in colon cancer cells was not explored. The present study investigated the anticancer activity of NSC735847 and four structurally similar analog in human tumorigenic (HT-29 and HCT-116) and non-tumorigenic (FHC) colon cell lines. NSC735847 was more cytotoxic toward tumorigenic than non-tumorigenic colonocytes. In addition, NSC735847 exhibited greater cytotoxicity and tumor selectivity than the NSC735847 derivatives. To gain insight into mechanisms of NSC735847 activity, the requirement for endoplasmic reticulum (ER) stress and oxidative stress was tested. The data show that ER stress played a key role in the cytotoxicity of NSC735847 while oxidative stress had little impact on cell fate. In addition, it was observed that the cytotoxic activity of NSC735847 required the presence of heme, but not iron. The activity of NSC735847 was then compared to clinically utilized CRC therapeutics. NSC735847 was cytotoxic toward colon tumor cells at lower concentrations than oxaliplatin (OX). In addition, cell death was achieved at lower concentrations in colon cancer cells that were co-treated with folinic acid (Fol), 5-FU (F), and NSC735847 (FolFNSC), than Fol, F, and OX (FolFOX). The selective activity of NSC735847 and its ability to induce cytotoxicity at low concentrations suggest that NSC735847 may be an alternative for oxaliplatin in the FolFOX regimen for patients who are unable to tolerate its adverse effects.
Identifiants
pubmed: 32626657
doi: 10.3389/fonc.2020.00965
pmc: PMC7313430
doi:
Types de publication
Journal Article
Langues
eng
Pagination
965Informations de copyright
Copyright © 2020 Elhassanny, Soliman, Marie, McGuire, Gul, ElSohly and Van Dross.
Références
Semin Cancer Biol. 2017 Oct;46:65-83
pubmed: 28254675
Biochem Pharmacol. 2017 Sep 1;139:56-70
pubmed: 28366726
Anticancer Res. 2013 Oct;33(10):4389-93
pubmed: 24123007
J Biol Chem. 2011 Jan 14;286(2):987-96
pubmed: 21059641
Angew Chem Int Ed Engl. 2016 Oct 24;55(44):13770-13774
pubmed: 27709833
Biochim Biophys Acta. 2013 Dec;1833(12):3460-3470
pubmed: 23850759
BMC Bioinformatics. 2017 Nov 29;18(1):529
pubmed: 29187165
Mol Cancer Ther. 2008 Aug;7(8):2528-35
pubmed: 18723497
Science. 2005 Feb 11;307(5711):935-9
pubmed: 15705855
Front Physiol. 2018 Nov 20;9:1595
pubmed: 30515102
Cancer Cell. 2014 May 12;25(5):563-73
pubmed: 24823636
Front Mol Neurosci. 2017 May 31;10:174
pubmed: 28620280
Trends Cancer. 2016 May;2(5):252-262
pubmed: 28741511
Malar J. 2018 Oct 17;17(1):369
pubmed: 30333022
Mol Carcinog. 2016 Nov;55(11):1807-1821
pubmed: 26513129
Nat Rev Drug Discov. 2009 Jul;8(7):579-91
pubmed: 19478820
Int J Cancer. 2009 Sep 15;125(6):1266-75
pubmed: 19533749
Mol Cancer Ther. 2017 May;16(5):838-849
pubmed: 28292936
PLoS One. 2017 Mar 15;12(3):e0173311
pubmed: 28296906
CA Cancer J Clin. 2019 Jan;69(1):7-34
pubmed: 30620402
J Hematol Oncol. 2018 Feb 20;11(1):23
pubmed: 29458389
ACS Chem Biol. 2016 Apr 15;11(4):882-8
pubmed: 26854499
Biochem Biophys Res Commun. 2006 Oct 27;349(3):1171-5
pubmed: 16970913
Am J Health Syst Pharm. 2013 Mar 1;70(5):395-406
pubmed: 23413162
Cancer Res. 2005 Oct 15;65(20):9517-24
pubmed: 16230417
Oncotarget. 2017 Jun 6;8(23):38022-38043
pubmed: 28410237
Integr Cancer Ther. 2004 Dec;3(4):349-80
pubmed: 15523106
Med Res Rev. 2017 Nov;37(6):1492-1517
pubmed: 28643446
Life Sci. 2001 Nov 21;70(1):49-56
pubmed: 11764006
Reprod Toxicol. 2016 Oct;65:194-203
pubmed: 27506918
Eur J Pharmacol. 2009 Dec 25;625(1-3):234-46
pubmed: 19835867
EBioMedicine. 2014 Nov 15;2(1):82-90
pubmed: 26137537
Free Radic Res. 2010 Nov;44(11):1289-95
pubmed: 20815780
ACS Cent Sci. 2017 Jul 26;3(7):743-750
pubmed: 28776016
Cancer Biol Ther. 2008 Jul;7(7):1017-23
pubmed: 18414062
N Engl J Med. 2004 Jun 3;350(23):2343-51
pubmed: 15175436
Anticancer Res. 2017 Nov;37(11):5995-6003
pubmed: 29061778
Free Radic Res. 2010 May;44(5):479-96
pubmed: 20370557
PLoS One. 2012;7(8):e42703
pubmed: 22900042
Free Radic Biol Med. 2004 Oct 1;37(7):998-1009
pubmed: 15336316
J Med Chem. 2016 Aug 25;59(16):7360-88
pubmed: 27010926
Ther Clin Risk Manag. 2005 Dec;1(4):249-58
pubmed: 18360567
Int J Biomed Sci. 2012 Mar;8(1):76-80
pubmed: 23675259
Curr Med Chem. 2017;24(15):1537-1557
pubmed: 28079003
Mol Cancer Ther. 2011 Sep;10(9):1709-19
pubmed: 21750216
Nucleic Acids Res. 2001 May 1;29(9):e45
pubmed: 11328886
Nat Rev Dis Primers. 2015 Nov 05;1:15065
pubmed: 27189416
Anticancer Res. 2004 Jul-Aug;24(4):2277-80
pubmed: 15330172
FEBS Lett. 1983 Aug 8;159(1-2):127-31
pubmed: 6688226
PLoS One. 2012;7(1):e29514
pubmed: 22276118
J Biol Chem. 2007 Mar 30;282(13):9372-82
pubmed: 17227762
Br J Pharmacol. 2001 Apr;132(8):1777-88
pubmed: 11309250
Invest New Drugs. 2011 Dec;29(6):1276-83
pubmed: 20607588
Clin Transl Gastroenterol. 2019 Jul;10(7):e00059
pubmed: 31259751
Oncoimmunology. 2017 Oct 4;6(12):e1386829
pubmed: 29209573
PLoS One. 2009 Oct 28;4(10):e7472
pubmed: 19862332
Malar J. 2014 Nov 26;13:463
pubmed: 25428624
Ann Oncol. 2010 May;21 Suppl 5:v70-7
pubmed: 20555107
Evid Based Complement Alternat Med. 2017;2017:7916031
pubmed: 28400846
Biochim Biophys Acta. 2014 Oct;1843(10):2143-9
pubmed: 24440276
Microb Cell. 2016 Apr 05;3(5):230-231
pubmed: 28357359
J Med Chem. 2012 Aug 23;55(16):7193-207
pubmed: 22827572
Angew Chem Int Ed Engl. 2007;46(33):6278-83
pubmed: 17640025
Cancer Cell. 2016 Jun 13;29(6):805-819
pubmed: 27238082
Cancer Res. 2005 Apr 15;65(8):3389-95
pubmed: 15833873
Malar J. 2015 Mar 29;14:135
pubmed: 25889242
Cancer Res. 2006 Aug 15;66(16):8182-91
pubmed: 16912197
Cell Biochem Biophys. 2015 Sep;73(1):137-45
pubmed: 25701954
J Biol Chem. 2011 Feb 25;286(8):6587-601
pubmed: 21149439
Prostaglandins Other Lipid Mediat. 2019 Jun;142:9-23
pubmed: 30858059