title: Cyclooxygenase-independent effects of aspirin on HT-29 human colon cancer cells, revealed by oligonucleotide microarrays.
abstract: 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.
authors.affiliation: Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Yin
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Zhao
authors.forename: Weiping
authors.initials: W
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis; D001241:Aspirin / Q000494:pharmacology*; D001709:Biotechnology / Q000379:methods; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000188:drug therapy*; D051546:Cyclooxygenase 2 / Q000494:pharmacology*; D016678:Genome; D019073:HT29 Cells; D006801:Humans; D008854:Microscopy, Electron; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010802:Phylogeny; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013778:Tetrazolium Salts; D013844:Thiazoles; D051546:Cyclooxygenase 2; C022616:thiazolyl blue; D001241:Aspirin