| Description: |
Previous work from our laboratory has identified R-flurbiprofen as a candidate chemopreventive agent for skin cancer. Despite our findings, and the investigation of R-flurbiprofen as a chemopreventive for prostate and colon cancer by other groups, the mechanism of action remains unclear. To gain mechanistic insight into these anti-proliferative effects, we carried out microarray analysis of HaCaT cells in response to both R-flurbiprofen and S-flurbiprofen treatment. This analysis shows that both R-flurbiprofen and S-flurbiprofen produced significant changes in gene expression compared to untreated control, however, no significant differences were identified between effects induced by the individual enantiomers. Many of the genes found to be altered compared to control are implicated in cellular growth, apoptosis and metastasis, a selection of which are discussed. The altered expression of these genes may contribute to the anti-proliferative effects of R-flurbiprofen and S-flurbiprofen. Keywords: oligonucleotide array, HaCaT, flurbiprofen, NSAID The study was designed as a triangular comparison, where RNA samples from both R-flurbiprofen and S-flurbiprofen treated cells would be compared to samples from untreated control cells to identify genes which were altered by the drugs. Additionally, direct comparison between samples from R-flurbiprofen treated cells and S-flurbiprofen treated cells would be carried out to facilitate identification of genes with different regulation between the two enantiomers. The Compugen 19k Human Oligo array was used to carry out this expression profiling. Array printing, sample labeling, hybridisation and data analysis were carried out by Adelaide Microarray Centre, where the Spot software package was used for data extraction and analysis. 3 arrays were used to compare R-flurbiprofen extracts to untreated controls, while 2 arrays each were used for comparison of S-flurbiprofen to control, and R-flurbiprofen to S-flurbiprofen.
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