Cyclooxygenase-independent effects of aspirin on HT-29 human colon cancer cells, revealed by oligonucleotide microarrays
- 157 Downloads
Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) inhibit proliferation of human colon cancer cells in vitro. Transmission electron microscope detected morphological features of apoptosis in the aspirin-treated (5 mM, 72 h) HT-29 cells in which cyclooxygenoase-2 is catalytically inactive. We investigated aspirin-induced genome-wide expression changes in HT-29 cells and further studied the time- and concentration-dependent expression changes in 374 apoptosis-related genes, which is the first to show stimulation of genome-wide expression of HT-29 cells by aspirin. The most marked effects of aspirin are on ribosome assembly and rRNA metabolism, which could explain why the quasi-apoptotic morphological changes are not accompanied by a classical DNA ladder. These findings demonstrate that aspirin induces apoptosis in HT-29 cells, bolstering the hypothesis that apoptosis may be a mechanism by which NSAIDs inhibit colon carcinogenesis.
KeywordsAspirin Apoptosis Colon cancer Cyclooxygenase-2 (COX-2) DNA microarray
Unable to display preview. Download preview PDF.
We thank Ch. Zhou, W. Shao, and L. Wang for helpful discussions and comments on the manuscript; Dr. D. Wright for his assistance with manuscript presentation; Dr. H. Smith for her review of the manuscript. This work was supported by grants from the Beijing Natural Science Foundation of China (No. H010210640121) and State Key Laboratory of Natural and Biomimetic Drugs (No. 0200006209089112565).
- Baron JA, Cole BF, Sandler RS, Haile RW, Ahnen D, Bresalier R, McKeown-Eyssen G, Summers RW, Rothstein R, Burke CA, Snover DC, Church TR, Allen JI, Beach M, Beck GJ, Bond JH, Byers T, Greenberg ER, Mandel JS, Marcon N, Mott LA, Pearson L, Saibil F, van Stolk RU (2003) A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 348:891–899PubMedCrossRefGoogle Scholar
- Marton MJ, DeRisi JL, Bennett HA, Iyer VR, Meyer MR, Roberts CJ, Stoughton R, Burchard J, Slade D, Dai H, Bassett Jr DE, Hartwell LH, Brown PO, Friend SH (1998) Drug target validation and identification of secondary drug target effects using DNA microarrays. Nat Med 4:1293–1301PubMedCrossRefGoogle Scholar