Aspirin and aspirin analogs on esophageal cancer

Rajagopal Sharada Kilari, Christopher J. Perry, Andrew Devitt, Stephen T. Safrany, Iain D. Nicholl

Research output: Contribution to journalMeeting abstract

Abstract

Background: Esophageal cancer is the eighth most common cancer seen worldwide and is the sixth most common cause of death from cancer. The UK alone has over 8,000 new cases of esophageal cancer every year. Epidemiological studies have shown that low-dose daily intake of aspirin can decrease the incidence of esophageal cancer. However, its use as an anti-cancer drug has been restrained because of its side effects exerted through inhibition of cyclooxygenase (COX) enzymes. In our study, we have investigated the effects of a number of novel aspirin analogs on esophageal cancer cell lines.
Methods: The effects of aspirin and its analogs on the viability of esophageal cancer cell lines were tested using the MTT assay. ApoSense and flow cytometric analysis were performed to examine whether aspirin analog-mediated tumor cell death is due to apoptosis or necrosis. Colorimetric assays measuring peroxidase component of cyclooxygenases were employed to screen aspirin analogs for COX inhibition.
Results: Our data suggests that the anti-proliferative property of certain aspirin analogs is greater than that of aspirin itself. Benzoylsalicylates and fumaroyl diaspirin were more effective than aspirin against the oe21 squamous cell carcinoma cells and oe33 esophageal adenocarcinoma cells. Flo-1 esophageal adenocarcinoma cells showed resistance to aspirin and most of the aspirin analogs other than the benzoylsalicylates. Both diaspirin and benzoylsalicylates inhibited metabolic activity in all these esophageal cells. However, apoptosis was induced in only a small proportion. We have also shown that these aspirin analogs do not appear to inhibit COX enzymes.
Conclusion: We have synthesized and characterized a number of novel aspirin analogs that are more effective against esophageal cancer cell lines than aspirin. These compounds do not exert their anti-proliferative effect through induction of apoptosis. Moreover, these analogs inability to inhibit COX enzymes suggests that they may cause fewer or no side effects compared to aspirin.
LanguageEnglish
Article numberAbstract 2527
Number of pages1
JournalCancer Research
Volume74
Issue number19 Supplement
DOIs
Publication statusPublished - 1 Oct 2014
EventAACR Annual Meeting 2014 - San Diego, CA, United States
Duration: 5 Apr 20149 Apr 2014

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Esophageal Neoplasms
Aspirin
Prostaglandin-Endoperoxide Synthases
Apoptosis
Cell Line
Neoplasms
Adenocarcinoma
Enzymes
Peroxidase
Epidemiologic Studies
Cause of Death
Squamous Cell Carcinoma
Cell Death
Necrosis

Bibliographical note

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA

Cite this

Kilari, R. S., Perry, C. J., Devitt, A., Safrany, S. T., & Nicholl, I. D. (2014). Aspirin and aspirin analogs on esophageal cancer. Cancer Research, 74(19 Supplement), [Abstract 2527]. https://doi.org/10.1158/1538-7445.AM2014-2527
Kilari, Rajagopal Sharada ; Perry, Christopher J. ; Devitt, Andrew ; Safrany, Stephen T. ; Nicholl, Iain D. / Aspirin and aspirin analogs on esophageal cancer. In: Cancer Research. 2014 ; Vol. 74, No. 19 Supplement.
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abstract = "Background: Esophageal cancer is the eighth most common cancer seen worldwide and is the sixth most common cause of death from cancer. The UK alone has over 8,000 new cases of esophageal cancer every year. Epidemiological studies have shown that low-dose daily intake of aspirin can decrease the incidence of esophageal cancer. However, its use as an anti-cancer drug has been restrained because of its side effects exerted through inhibition of cyclooxygenase (COX) enzymes. In our study, we have investigated the effects of a number of novel aspirin analogs on esophageal cancer cell lines.Methods: The effects of aspirin and its analogs on the viability of esophageal cancer cell lines were tested using the MTT assay. ApoSense and flow cytometric analysis were performed to examine whether aspirin analog-mediated tumor cell death is due to apoptosis or necrosis. Colorimetric assays measuring peroxidase component of cyclooxygenases were employed to screen aspirin analogs for COX inhibition.Results: Our data suggests that the anti-proliferative property of certain aspirin analogs is greater than that of aspirin itself. Benzoylsalicylates and fumaroyl diaspirin were more effective than aspirin against the oe21 squamous cell carcinoma cells and oe33 esophageal adenocarcinoma cells. Flo-1 esophageal adenocarcinoma cells showed resistance to aspirin and most of the aspirin analogs other than the benzoylsalicylates. Both diaspirin and benzoylsalicylates inhibited metabolic activity in all these esophageal cells. However, apoptosis was induced in only a small proportion. We have also shown that these aspirin analogs do not appear to inhibit COX enzymes.Conclusion: We have synthesized and characterized a number of novel aspirin analogs that are more effective against esophageal cancer cell lines than aspirin. These compounds do not exert their anti-proliferative effect through induction of apoptosis. Moreover, these analogs inability to inhibit COX enzymes suggests that they may cause fewer or no side effects compared to aspirin.",
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Kilari, RS, Perry, CJ, Devitt, A, Safrany, ST & Nicholl, ID 2014, 'Aspirin and aspirin analogs on esophageal cancer' Cancer Research, vol. 74, no. 19 Supplement, Abstract 2527. https://doi.org/10.1158/1538-7445.AM2014-2527

Aspirin and aspirin analogs on esophageal cancer. / Kilari, Rajagopal Sharada; Perry, Christopher J.; Devitt, Andrew; Safrany, Stephen T.; Nicholl, Iain D.

In: Cancer Research, Vol. 74, No. 19 Supplement, Abstract 2527, 01.10.2014.

Research output: Contribution to journalMeeting abstract

TY - JOUR

T1 - Aspirin and aspirin analogs on esophageal cancer

AU - Kilari, Rajagopal Sharada

AU - Perry, Christopher J.

AU - Devitt, Andrew

AU - Safrany, Stephen T.

AU - Nicholl, Iain D.

N1 - Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Background: Esophageal cancer is the eighth most common cancer seen worldwide and is the sixth most common cause of death from cancer. The UK alone has over 8,000 new cases of esophageal cancer every year. Epidemiological studies have shown that low-dose daily intake of aspirin can decrease the incidence of esophageal cancer. However, its use as an anti-cancer drug has been restrained because of its side effects exerted through inhibition of cyclooxygenase (COX) enzymes. In our study, we have investigated the effects of a number of novel aspirin analogs on esophageal cancer cell lines.Methods: The effects of aspirin and its analogs on the viability of esophageal cancer cell lines were tested using the MTT assay. ApoSense and flow cytometric analysis were performed to examine whether aspirin analog-mediated tumor cell death is due to apoptosis or necrosis. Colorimetric assays measuring peroxidase component of cyclooxygenases were employed to screen aspirin analogs for COX inhibition.Results: Our data suggests that the anti-proliferative property of certain aspirin analogs is greater than that of aspirin itself. Benzoylsalicylates and fumaroyl diaspirin were more effective than aspirin against the oe21 squamous cell carcinoma cells and oe33 esophageal adenocarcinoma cells. Flo-1 esophageal adenocarcinoma cells showed resistance to aspirin and most of the aspirin analogs other than the benzoylsalicylates. Both diaspirin and benzoylsalicylates inhibited metabolic activity in all these esophageal cells. However, apoptosis was induced in only a small proportion. We have also shown that these aspirin analogs do not appear to inhibit COX enzymes.Conclusion: We have synthesized and characterized a number of novel aspirin analogs that are more effective against esophageal cancer cell lines than aspirin. These compounds do not exert their anti-proliferative effect through induction of apoptosis. Moreover, these analogs inability to inhibit COX enzymes suggests that they may cause fewer or no side effects compared to aspirin.

AB - Background: Esophageal cancer is the eighth most common cancer seen worldwide and is the sixth most common cause of death from cancer. The UK alone has over 8,000 new cases of esophageal cancer every year. Epidemiological studies have shown that low-dose daily intake of aspirin can decrease the incidence of esophageal cancer. However, its use as an anti-cancer drug has been restrained because of its side effects exerted through inhibition of cyclooxygenase (COX) enzymes. In our study, we have investigated the effects of a number of novel aspirin analogs on esophageal cancer cell lines.Methods: The effects of aspirin and its analogs on the viability of esophageal cancer cell lines were tested using the MTT assay. ApoSense and flow cytometric analysis were performed to examine whether aspirin analog-mediated tumor cell death is due to apoptosis or necrosis. Colorimetric assays measuring peroxidase component of cyclooxygenases were employed to screen aspirin analogs for COX inhibition.Results: Our data suggests that the anti-proliferative property of certain aspirin analogs is greater than that of aspirin itself. Benzoylsalicylates and fumaroyl diaspirin were more effective than aspirin against the oe21 squamous cell carcinoma cells and oe33 esophageal adenocarcinoma cells. Flo-1 esophageal adenocarcinoma cells showed resistance to aspirin and most of the aspirin analogs other than the benzoylsalicylates. Both diaspirin and benzoylsalicylates inhibited metabolic activity in all these esophageal cells. However, apoptosis was induced in only a small proportion. We have also shown that these aspirin analogs do not appear to inhibit COX enzymes.Conclusion: We have synthesized and characterized a number of novel aspirin analogs that are more effective against esophageal cancer cell lines than aspirin. These compounds do not exert their anti-proliferative effect through induction of apoptosis. Moreover, these analogs inability to inhibit COX enzymes suggests that they may cause fewer or no side effects compared to aspirin.

UR - http://cancerres.aacrjournals.org/content/74/19_Supplement/2527

U2 - 10.1158/1538-7445.AM2014-2527

DO - 10.1158/1538-7445.AM2014-2527

M3 - Meeting abstract

VL - 74

JO - Cancer Research

T2 - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 19 Supplement

M1 - Abstract 2527

ER -

Kilari RS, Perry CJ, Devitt A, Safrany ST, Nicholl ID. Aspirin and aspirin analogs on esophageal cancer. Cancer Research. 2014 Oct 1;74(19 Supplement). Abstract 2527. https://doi.org/10.1158/1538-7445.AM2014-2527