{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:56:35Z","timestamp":1761058595296},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,12,27]],"date-time":"2006-12-27T00:00:00Z","timestamp":1167177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neovascularization is an essential process in tumor development, it is conceivable that anti\u2010angiogenic treatment may block tumor growth. In angiogenesis, nitric oxide (NO) is an important factor which mediates vascular endothelial cell growth and migration. \u03b2\u2010Lapachone (3,4\u2010dihydro\u20102,2\u2010dimethyl\u20102H\u2010naphtho\u2010[1,2\u2010b]pyran\u20105,6\u2010dione), a natural product extracted from the lapacho tree (<jats:italic>Tabebuia avellanedae<\/jats:italic>), has been demonstrated to possess anti\u2010cancer and anti\u2010viral effects. Whether \u03b2\u2010lapachone can induce endothelial cell death or has an anti\u2010angiogenic effect is still an enigma. We investigated the in vitro effect of \u03b2\u2010lapachone on endothelial cells, including human vascular endothelial cell line, EAhy926, and human umbilical vascular endothelial cells (HUVEC). Our results revealed that (1) the intracellular cGMP levels and the mitochondria membrane potential (MMP) decreased, and calpain and caspases were activated, during \u03b2\u2010lapachone\u2010induced endothelial cell death; (2) co\u2010treatment with calpain inhibitors (ALLM or ALLN) or the intracellular calcium chelator, BAPTA, but not the general caspase inhibitor, zVAD\u2010fmk, provided significant protection against apoptosis by preventing the \u03b2\u2010lapachone\u2010induced MMP decrease and cytoplasmic calcium increase; (3) addition of NO downregulated the \u03b2\u2010lapachone\u2010induced cGMP depletion and protected the cells from apoptosis by blocking the MMP decrease and the calcium increase; and (4) exogenous NO protects endothelial cells against the cell death induced by \u03b2\u2010lapachone, but not the anti\u2010angiogenic effect. From all the data above, we demonstrated that NO can attenuate the apoptotic effect of \u03b2\u2010lapachone on human endothelial cells and suggest that \u03b2\u2010lapachone may have potential as an anti\u2010angiogenic drug. J. Cell. Physiol. 211: 522\u2013532, 2007. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.20963","type":"journal-article","created":{"date-parts":[[2006,12,27]],"date-time":"2006-12-27T16:17:30Z","timestamp":1167236250000},"page":"522-532","source":"Crossref","is-referenced-by-count":26,"title":["Involvement of NO\/cGMP signaling in the apoptotic and anti\u2010angiogenic effects of \u03b2\u2010lapachone on endothelial cells in vitro"],"prefix":"10.1002","volume":"211","author":[{"given":"Hsiu\u2010Ni","family":"Kung","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung\u2010Liang","family":"Chien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gar\u2010Yang","family":"Chau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming\u2010Jaw","family":"Don","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuo\u2010Shyan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yat\u2010Pang","family":"Chau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,12,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00192885"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.202.6.645"},{"key":"e_1_2_5_4_1","first-page":"605","article-title":"Inhibition 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