{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:49:22Z","timestamp":1790790562815,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2007,12,12]],"date-time":"2007-12-12T00:00:00Z","timestamp":1197417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2008,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nitroxyl (HNO) can inhibit the glycolytic enzyme glyceraldehyde 3\u2010phosphate dehydrogenase (GAPDH). Because of the importance of glycolysis in many malignant cells, we thus propose that HNO can adversely affect tumor growth. This hypothesis was tested using <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> models of breast cancer. We report here for the first time that HNO suppresses the proliferation of both estrogen receptor (ER)\u2010positive and ER\u2010negative human breast cancer cell lines, in a dose dependent manner. Mice treated with HNO either injected into the tumor itself or <jats:italic>via<\/jats:italic> the intraperitoneal approach had smaller xenograft tumor size. In addition to significantly decreased blood vessel density in the HNO\u2010treated tumors, we observed lower levels of circulating serum vascular endothelial growth factor (VEGF). Accordingly, there was a decrease in total HIF\u20101\u03b1 (hypoxia\u2010inducible factor) protein in HNO\u2010treated tumor cells. Further studies showed inhibition of GAPDH activity in HNO\u2010treated human breast cancer cell lines and in HNO\u2010treated tumor tissue derived from xenografts. One explanation for the multiplicity of actions observed after HNO treatment could be the effect from the initial inhibition of GAPDH, providing a potential therapeutic avenue based upon blocking glycolysis resulting in decreased HIF\u20101\u03b1, thus leading to angiogenesis inhibition. Therefore, HNO appears to act <jats:italic>via<\/jats:italic> mechanism(s) different from those of existing breast cancer drugs, making it a potential candidate to overcome known and emerging drug resistance pathways. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23305","type":"journal-article","created":{"date-parts":[[2007,12,12]],"date-time":"2007-12-12T18:48:31Z","timestamp":1197485311000},"page":"1905-1910","source":"Crossref","is-referenced-by-count":92,"title":["Nitroxyl inhibits breast tumor growth and angiogenesis"],"prefix":"10.1002","volume":"122","author":[{"given":"Andrew J.","family":"Norris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam 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