Title:The Cytotoxicity and Synergistic Potential of Aspirin and Aspirin Analogues Towards Oesophageal and Colorectal Cancer
Volume: 14
Issue: 2
Author(s): Rajagopal S. Kilari, Asma’u I.J. Bashir, Andreue Devitt, Christopher J. Perry, Stephen T. Safrany and Iain D. Nicholl*
Affiliation:
- Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton WV1 1 LY,United Kingdom
Keywords:
Oesophageal cancer, platins, aspirin, aspirin analogues, apoptosis, morbidity.
Abstract:
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.
