Cyclooxygenase-independent effects of aspirin on HT-29 human colon cancer cells, revealed by oligonucleotide microarrays
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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
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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).
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