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Recently, the reduced form of NO\u2013 (protonated as HNO, nitroxyl, azanone, isoelectronic with O2) has also emerged as a candidate for therapeutic applications including treatment of acute heart failure and alcoholism. Here, we show that HNO is a product of the reaction of the RuII complex [Ru(bpy)2(SO3)(NO)]+ (1) with glutathione or N-acetyl-L-cysteine, using met-myoglobin and carboxy-PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) as trapping agents. Characteristic absorption spectroscopic profiles for HNO reactions with met-myoglobin were obtained, as well as EPR evidence from carboxy-PTIO experiments. Importantly, the product HNO counteracted NO-induced as well as hypoxia-induced stabilization of the tumor-suppressor HIF-1\u03b1 in cancer cells. The functional disruption of neovascularization by HNO produced by this metallonitrosyl complex was demonstrated in an in vitro angiogenesis model. This behavior is consistent with HNO biochemistry and contrasts with NO-mediated stabilization of HIF-1\u03b1. Together, these results demonstrate for the first time thiol-dependent production of HNO by a ruthenium complex and subsequent destabilization of HIF-1\u03b1. This work suggests that the complex warrants further investigation as a promising antiangiogenesis agent for the treatment of cancer.<\/jats:p>","DOI":"10.1021\/acschembio.6b00222","type":"journal-article","created":{"date-parts":[[2016,5,18]],"date-time":"2016-05-18T10:08:40Z","timestamp":1463566120000},"page":"2057-2065","source":"Crossref","is-referenced-by-count":49,"title":["Thiol-Activated HNO Release from a Ruthenium Antiangiogenesis\nComplex and HIF-1\u03b1 Inhibition for Cancer Therapy"],"prefix":"10.1021","volume":"11","author":[{"given":"Eduardo Henrique","family":"Silva Sousa","sequence":"first","affiliation":[{"name":"Federal University of Ceara\u0301 , , Mister Hull Avenue, Building 935 , ,","place":["Fortaleza, Brazil, 60455-760"]},{"name":"University of Warwick , , ,","place":["Coventry, United Kingdom, CV4 7AL"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Ridnour","sequence":"additional","affiliation":[{"name":"National Cancer Institute , , , ,","place":["Frederick, Maryland, United States, 21702"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Flore\u0302ncio S.","family":"Gouveia","sequence":"additional","affiliation":[{"name":"Federal University of Ceara\u0301 , , Mister Hull Avenue, Building 935 , ,","place":["Fortaleza, Brazil, 60455-760"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Daniel","family":"Silva da Silva","sequence":"additional","affiliation":[{"name":"Federal University of Ceara\u0301 , , Mister Hull Avenue, Building 935 , ,","place":["Fortaleza, Brazil, 60455-760"]},{"name":"Federal Institute of Bahia , , , ,","place":["Salvador, Brazil, 40301-150"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Wink","sequence":"additional","affiliation":[{"name":"National Cancer Institute , , , ,","place":["Frederick, Maryland, United States, 21702"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Gonzaga","family":"de Franc\u0327a Lopes","sequence":"additional","affiliation":[{"name":"Federal University of Ceara\u0301 , , Mister Hull Avenue, Building 935 , ,","place":["Fortaleza, Brazil, 60455-760"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Sadler","sequence":"additional","affiliation":[{"name":"University of Warwick , , ,","place":["Coventry, United Kingdom, CV4 7AL"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2016,5,18]]},"reference":[{"key":"2026090316312744200_cit1","volume-title":"Nitric Oxide:Biology and Pathobiology","author":"Lincoln","year":"2000"},{"key":"2026090316312744200_cit2","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.niox.2008.05.003","article-title":"The reemergence\nof nitric oxide in cancer","volume":"19","author":"Wink","year":"2008","journal-title":"Nitric Oxide"},{"key":"2026090316312744200_cit3","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.niox.2014.05.014","article-title":"Hydrogen sulfide and nitric oxide interactions in inflammation","volume":"41","author":"Lo Faro","year":"2014","journal-title":"Nitric Oxide"},{"key":"2026090316312744200_cit4","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.freeradbiomed.2008.03.020","article-title":"The chemical biology of nitric oxide:\nimplications in cellular signaling","volume":"45","author":"Thomas","year":"2008","journal-title":"Free Radical\nBiol. 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