{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:17:38Z","timestamp":1790918258138,"version":"4.1.0"},"reference-count":25,"publisher":"National Academy of Sciences","issue":"47","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,11,22]]},"abstract":"<jats:p>\n                    Nitric oxide-donating aspirin (NO-ASA) is a promising chemoprevention agent against colon cancer and other cancers. It consists of traditional ASA to which a NO-releasing moiety is bound through a spacer. NO-ASA inhibits colon cancer cell growth several hundred times more potently than does ASA. In\n                    <jats:italic>Min<\/jats:italic>\n                    mice, NO-ASA inhibited intestinal carcinogenesis without affecting cell proliferation. Thus, we examined whether NO-ASA's most important cell kinetic effect is the induction of apoptosis. After confirming induction of apoptosis in\n                    <jats:italic>Min<\/jats:italic>\n                    mice, we studied the underlying mechanism in human colon adenocarcinoma cells. NO-ASA's spacer formed a conjugate with glutathione, depleting glutathione stores. This induced oxidative stress (increased intracellular levels of peroxides and\n                    <jats:inline-formula>\n                      <jats:tex-math notation=\"LaTeX\">\\documentclass[12pt]{minimal}\n\\usepackage{amsmath}\n\\usepackage{wasysym} \n\\usepackage{amsfonts} \n\\usepackage{amssymb} \n\\usepackage{amsbsy}\n\\usepackage{mathrsfs}\n\\setlength{\\oddsidemargin}{-69pt}\n\\begin{document}\n\\begin{equation*}{\\mathrm{O}}_{2}^{{\\cdot}-}\\end{equation*}\\end{document}<\/jats:tex-math>\n                    <\/jats:inline-formula>\n                    ) leads to apoptosis by activating the intrinsic apoptosis pathway. NO-ASA disrupted adherens junctions by inducing cleavage of \u03b2- and \u03b3-catenin, resulting in cell detachment. NO-ASA inhibited Wnt signaling by a dual mechanism: at low concentrations it blocked the formation of \u03b2-catenin\/Tcf complexes (dominant mechanism), and at higher concentrations it also cleaved \u03b2-catenin. These findings provide a mechanism of action by a potent chemopreventive agent, underscore the significance of these pathways in regulating cell death in the context of cancer chemoprevention, and present a paradigm for developing agents with enhanced cancer cell growth inhibitory properties.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0506893102","type":"journal-article","created":{"date-parts":[[2005,11,10]],"date-time":"2005-11-10T20:33:38Z","timestamp":1131654818000},"page":"17207-17212","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":110,"title":["Nitric oxide-donating aspirin induces apoptosis in human colon cancer cells through induction of oxidative stress"],"prefix":"10.1073","volume":"102","author":[{"given":"Jianjun","family":"Gao","sequence":"first","affiliation":[{"name":"Division of Cancer Prevention, Department of Medicine, Stony Brook University, Stony Brook, NY 11794-5200"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention, Department of Medicine, Stony Brook University, Stony Brook, NY 11794-5200"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basil","family":"Rigas","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention, Department of Medicine, Stony Brook University, Stony Brook, NY 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