Aspirin and alterations in DNA repair proteins in the SW480 colorectal cancer cell line.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractRegular aspirin intake is associated with a reduction in the incidence of colorectal cancer. Aspirin has been shown to be cytotoxic to colorectal cancer cells in vitro. The molecular basis for this cytotoxicity is controversial, with a number of competing hypotheses in circulation. One suggestion is that the protective effect is related to the induction of expression of the DNA mismatch repair (MMR) proteins hMLH1, hMSH2, hMSH6 and hPMS2 in DNA MMR proficient cells. We report that treatment of the DNA MMR competent/p53 mutant colorectal cancer cell line SW480 with 1 mM aspirin for 48 h caused changes in mRNA expression of several key genes involved in DNA damage signalling pathways, including a significant down-regulation in transcription of the genes ATR, BRCA1 and MAPK12. Increases in the transcription of XRCC3 and GADD45alpha genes are also reported. Regulation of these genes could potentially have profound effects on colorectal cancer cells and may play a role in the observed chemo-protective effect of aspirin in vivo. Although a correlation was not seen between transcript and protein levels of ATR, BRCA1 and GADD45alpha, an increase in XRCC3 encoded protein expression upon aspirin treatment in SW480 cells was observed by immunoblotting, immunofluorescence and immunohistochemical analysis. This is the first report of XRCC3 gene transcription and encoded protein expression being susceptible to exposure to the non-steroidal anti-inflammatory drug, aspirin. Furthermore, this study indicates that alterations in gene transcription seen in microarray studies must be verified at the protein level.
CitationOncology reports, 24 (1):37-46
- Expression profile analysis of colon cancer cells in response to sulindac or aspirin.
- Authors: Iizaka M, Furukawa Y, Tsunoda T, Akashi H, Ogawa M, Nakamura Y
- Issue date: 2002 Mar 29
- DNA array analysis of the effects of aspirin on colon cancer cells: involvement of Rac1.
- Authors: Hardwick JC, van Santen M, van den Brink GR, van Deventer SJ, Peppelenbosch MP
- Issue date: 2004 Jul
- Coordinate alterations in the expression of BRCA1, BRCA2, p300, and Rad51 in response to genotoxic and other stresses in human prostate cancer cells.
- Authors: Yuan R, Fan S, Wang JA, Meng Q, Ma Y, Schreiber D, Goldberg ID, Rosen EM
- Issue date: 1999 Jun 15
- Expression of the mismatch repair gene hMSH2 in sporadic colorectal cancer.
- Authors: Maeda K, Nishiguchi Y, Onoda N, Otani H, Nakata B, Yamada S, Okuno M, Sowa M, Chung KH
- Issue date: 1998 Dec
- Anticancer activity of litchi fruit pericarp extract against human breast cancer in vitro and in vivo.
- Authors: Wang X, Yuan S, Wang J, Lin P, Liu G, Lu Y, Zhang J, Wang W, Wei Y
- Issue date: 2006 Sep 1