The Cytotoxicity and Synergistic Potential of Aspirin and Aspirin Analogues Towards Oesophageal and Colorectal Cancer.
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Aspirin
/ analogs & derivatives
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cisplatin
/ pharmacology
Colorectal Neoplasms
/ drug therapy
Drug Synergism
Esophageal Neoplasms
/ drug therapy
Humans
Organoplatinum Compounds
/ pharmacology
Oxaliplatin
/ pharmacology
Oesophageal cancer
apoptosis
aspirin
aspirin analogues
morbidity
platins.
Journal
Current clinical pharmacology
ISSN: 2212-3938
Titre abrégé: Curr Clin Pharmacol
Pays: United Arab Emirates
ID NLM: 101273158
Informations de publication
Date de publication:
2019
2019
Historique:
received:
13
04
2018
revised:
24
10
2018
accepted:
31
10
2018
pubmed:
13
11
2018
medline:
8
7
2020
entrez:
13
11
2018
Statut:
ppublish
Résumé
Oesophageal cancer (OC) is a deadly cancer because of its aggressive nature with survival rates that have barely improved in decades. Epidemiologic studies have shown that low-dose daily intake of aspirin can decrease the incidence of OC. The toxicity of aspirin and aspirin derivatives to OC and a CRC cell line were investigated in the presence and absence of platins. The data in this study show the effects of a number of aspirin analogues and aspirin on OC cell lines that originally presented as squamous cell carcinoma (SSC) and adenocarcinoma (ADC). The aspirin analogues fumaryldiaspirin (PN517) and the benzoylsalicylates (PN524, PN528 and PN529), were observed to be more toxic against the OC cell lines than aspirin. Both quantitative and qualitative apoptosis experiments reveal that these compounds largely induce apoptosis, although some necrosis was evident with PN528 and PN529. Failure to recover following the treatment with these analogues emphasized that these drugs are largely cytotoxic in nature. The OE21 (SSC) and OE33 (ADC) cell lines were more sensitive to the aspirin analogues compared to the Flo-1 cell line (ADC). A non-cancerous oesophageal primary cells NOK2101, was used to determine the specificity of the aspirin analogues and cytotoxicity assays revealed that analogues PN528 and PN529 were selectively toxic to cancer cell lines, whereas PN508, PN517 and PN524 also induced cell death in NOK2101. In combination index testing synergistic interactions of the most promising compounds, including aspirin, with cisplatin, oxaliplatin and carboplatin against the OE33 cell line and the SW480 colorectal cancer (CRC) cell line were investigated. Compounds PN517 and PN524, and to a lesser extent PN528, synergised with cisplatin against OE33 cells. Cisplatin and oxaliplatin synergised with aspirin and PN517 when tested against the SW480 cell line. These findings indicate the potential and limitations of aspirin and aspirin analogues as chemotherapeutic agents against OC and CRC when combined with platins.
Sections du résumé
BACKGROUND
Oesophageal cancer (OC) is a deadly cancer because of its aggressive nature with survival rates that have barely improved in decades. Epidemiologic studies have shown that low-dose daily intake of aspirin can decrease the incidence of OC.
METHODS
The toxicity of aspirin and aspirin derivatives to OC and a CRC cell line were investigated in the presence and absence of platins.
RESULTS
The data in this study show the effects of a number of aspirin analogues and aspirin on OC cell lines that originally presented as squamous cell carcinoma (SSC) and adenocarcinoma (ADC). The aspirin analogues fumaryldiaspirin (PN517) and the benzoylsalicylates (PN524, PN528 and PN529), were observed to be more toxic against the OC cell lines than aspirin. Both quantitative and qualitative apoptosis experiments reveal that these compounds largely induce apoptosis, although some necrosis was evident with PN528 and PN529. Failure to recover following the treatment with these analogues emphasized that these drugs are largely cytotoxic in nature. The OE21 (SSC) and OE33 (ADC) cell lines were more sensitive to the aspirin analogues compared to the Flo-1 cell line (ADC). A non-cancerous oesophageal primary cells NOK2101, was used to determine the specificity of the aspirin analogues and cytotoxicity assays revealed that analogues PN528 and PN529 were selectively toxic to cancer cell lines, whereas PN508, PN517 and PN524 also induced cell death in NOK2101. In combination index testing synergistic interactions of the most promising compounds, including aspirin, with cisplatin, oxaliplatin and carboplatin against the OE33 cell line and the SW480 colorectal cancer (CRC) cell line were investigated. Compounds PN517 and PN524, and to a lesser extent PN528, synergised with cisplatin against OE33 cells. Cisplatin and oxaliplatin synergised with aspirin and PN517 when tested against the SW480 cell line.
CONCLUSION
These findings indicate the potential and limitations of aspirin and aspirin analogues as chemotherapeutic agents against OC and CRC when combined with platins.
Identifiants
pubmed: 30417794
pii: CCP-EPUB-94452
doi: 10.2174/1574884713666181112141151
pmc: PMC7040498
doi:
Substances chimiques
Antineoplastic Agents
0
Organoplatinum Compounds
0
Oxaliplatin
04ZR38536J
Cisplatin
Q20Q21Q62J
Aspirin
R16CO5Y76E
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
141-151Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Références
Eur J Clin Invest. 2002 Nov;32(11):838-46
pubmed: 12423325
J Gastroenterol Hepatol. 2004 Jun;19(6):638-42
pubmed: 15151617
Cancer Res. 2014 Nov 1;74(21):5948-54
pubmed: 25145669
Cancer Res. 2010 Sep 1;70(17):6787-96
pubmed: 20647328
Carcinogenesis. 2009 Jul;30(7):1073-81
pubmed: 19468060
Semin Radiat Oncol. 2007 Jan;17(1):38-44
pubmed: 17185196
Oncogene. 1999 Dec 20;18(55):7908-16
pubmed: 10630643
Science. 2012 May 18;336(6083):918-22
pubmed: 22517326
Cancer Res. 1997 Dec 15;57(24):5571-8
pubmed: 9407969
FASEB J. 1997 Mar;11(4):234-47
pubmed: 9068612
Cancer Res. 2003 Mar 1;63(5):906-11
pubmed: 12615701
Nat Rev Cancer. 2010 Feb;10(2):87-101
pubmed: 20094044
Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):2869-73
pubmed: 9096313
Curr Oncol. 2011 Jan;18(1):18-25
pubmed: 21331278
PLoS Genet. 2013 Jun;9(6):e1003553
pubmed: 23785299
Carcinogenesis. 2009 Mar;30(3):377-86
pubmed: 19136477
Cancer Res. 2005 May 1;65(9):3735-44
pubmed: 15867369
Nature. 1998 Nov 5;396(6706):77-80
pubmed: 9817203
Cancer Epidemiol Biomarkers Prev. 1998 Feb;7(2):97-102
pubmed: 9488582
Circulation. 2017 Sep 26;136(13):1183-1192
pubmed: 28947478
Thromb Res. 2003 Jun 15;110(5-6):255-8
pubmed: 14592543
Biomed Rep. 2014 May;2(3):344-348
pubmed: 24748972
Lancet Oncol. 2005 Dec;6(12):945-52
pubmed: 16321762
Cancer Res. 2007 Feb 15;67(4):1660-9
pubmed: 17308107
Gastroenterology. 2012 Jun;142(7):1504-15.e3
pubmed: 22406476
J Immunol Methods. 1983 Dec 16;65(1-2):55-63
pubmed: 6606682
Br J Cancer. 1997;75(2):258-63
pubmed: 9010035
Lancet. 2009 Apr 11;373(9671):1301-9
pubmed: 19328542
Mol Carcinog. 2010 Mar;49(3):235-46
pubmed: 19908241
Front Oncol. 2013 Jul 11;3:181
pubmed: 23875171
Gastroenterology. 2000 Mar;118(3):487-96
pubmed: 10702199
Oncol Rep. 2011 Sep;26(3):557-65
pubmed: 21617874
Cancer Res. 1993 Mar 15;53(6):1322-7
pubmed: 8443812
Ann Oncol. 2015 Jan;26(1):47-57
pubmed: 25096604
Adv Enzyme Regul. 1984;22:27-55
pubmed: 6382953
J Natl Cancer Inst. 1984 Mar;72(3):705-7
pubmed: 6583454
Elife. 2016 May 31;5:
pubmed: 27244239
Science. 1994 Aug 12;265(5174):956-9
pubmed: 8052854
Gastroenterology. 2003 Jan;124(1):47-56
pubmed: 12512029
Cancer Res. 1999 Jan 1;59(1):198-204
pubmed: 9892207
Methods Mol Biol. 2011;731:421-34
pubmed: 21516426
Cancer Res. 2010 Jan 15;70(2):440-6
pubmed: 20068163
J Immunol Methods. 1995 Jul 17;184(1):39-51
pubmed: 7622868
FASEB J. 2001 Oct;15(12):2057-72
pubmed: 11641233
Gut. 2013 Oct;62(10):1406-14
pubmed: 22917659
Cancer Res. 1998 Jul 15;58(14):2929-34
pubmed: 9679948
Cancer. 1995 Oct 1;76(7):1116-9
pubmed: 8630885
N Engl J Med. 2012 Oct 25;367(17):1596-606
pubmed: 23094721
Pharmacol Rev. 2006 Sep;58(3):621-81
pubmed: 16968952
J Biol Chem. 1980 Apr 10;255(7):2816-21
pubmed: 7358711
Ann Oncol. 2012 Jun;23(6):1403-15
pubmed: 22517822
Am Fam Physician. 2006 Jun 15;73(12):2187-94
pubmed: 16836035
Br J Cancer. 2004 Jul 19;91(2):381-8
pubmed: 15188000
Oncol Rep. 2014 Oct;32(4):1670-80
pubmed: 25109257
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Oncol Rep. 2010 Jan;23(1):121-8
pubmed: 19956872
Oncol Rep. 2010 Jun;23(6):1735-45
pubmed: 20428833
Biochem Pharmacol. 2007 Aug 1;74(3):392-406
pubmed: 17559811