Effects of Thymidylate Synthase Inhibition on Cancer Cells
Author Information
Author(s): Webley S D, Welsh S J, Jackman A L, Aherne G W
Primary Institution: CRC Centre for Cancer Therapeutics, Institute of Cancer Research
Hypothesis
The study investigates the relationship between loss of viability following thymidylate synthase inhibition and dUTP accumulation in cancer cells.
Conclusion
The study found that dUTP accumulation is linked to an earlier loss of viability in cancer cells following thymidylate synthase inhibition.
Supporting Evidence
- Cell cycle arrest was an early event in all cell lines following TS inhibition.
- A549 cells showed exacerbated DNA damage due to higher activity of uracil-DNA glycosylase.
- Transfection of dUTPase into HT29 cells reduced cytotoxicity after 24 hours of exposure to ZD9331.
Takeaway
When cancer cells are treated with a certain drug, they can die faster if they build up a specific molecule called dUTP.
Methodology
The study used human lung and colon tumor cell lines to examine the effects of thymidylate synthase inhibition on cell viability and dUTP accumulation.
Digital Object Identifier (DOI)
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