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In order to elucidate the underlying mechanisms on a molecular basis, we used HT\u201029 human colon carcinoma cells, carrying a <jats:italic>p53<\/jats:italic> loss\u2010of\u2010function mutation, and examined the effects of NO on apoptosis when induced either by the flavonoid flavone or by the chemotherapeutic drug camptothecin (CPT), which is able to scavenge NO by superoxide anion production. Caspase\u20103 activation as well as nuclear fragmentation, both indicative of apoptosis, were dose dependently inhibited by the NO\u2010liberating agents sodium nitroprusside (SNP) or S\u2010nitroso\u2010N\u2010acetyl\u2010D,L\u2010penicillamine (SNAP) when apoptosis was initiated by flavone with only minor effects on apoptosis when initiated by camptothecin. The transcript levels of 9 apoptosis\u2010related genes were assessed and NO liberation was shown to completely and specifically prevent the flavone\u2010induced but not camptothecin\u2010induced decrease in bcl\u2010X<jats:sub>L<\/jats:sub> mRNA levels. These results were also confirmed at the protein level. The effects of NO on the mitochondrial apoptosis pathway were further evidenced by the scavenging of superoxide anions as produced in mitochondria of cells undergoing apoptosis. Scavenging of mitochondrial superoxide anions by NO prevents the downregulation of bcl\u2010X<jats:sub>L<\/jats:sub>, the depolarization of the mitochondrial membrane potential, the cytochrome c release and finally the activation of caspase\u20103. In conclusion, NO effectively inhibits apoptosis by scavenging superoxide anions generated in the mitochondria of <jats:italic>p53<\/jats:italic> mutant cells and thereby prevents the downregulation of the antiapoptotic factor bcl\u2010X<jats:sub>L<\/jats:sub>, which controls the mitochondrial apoptosis pathway. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.11294","type":"journal-article","created":{"date-parts":[[2003,7,11]],"date-time":"2003-07-11T10:07:05Z","timestamp":1057918025000},"page":"666-675","source":"Crossref","is-referenced-by-count":51,"title":["Nitric oxide suppresses apoptosis in human colon cancer cells by scavenging mitochondrial superoxide 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