{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T11:49:41Z","timestamp":1770983381518,"version":"3.50.1"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1995,3,15]]},"abstract":"<jats:p>An indazole derivative, YC-1, was identified in this study to be capable of reversibly and effectively inhibiting proliferation of rat A10 vascular smooth-muscle cells (VSMCs) in vitro. YC-1 (1-100 microM) dose-dependently inhibited [3H]thymidine incorporation into DNA in rat A10 VSMCs that were synchronized by serum depletion and then restimulated by addition of 10% foetal calf serum (FCS), whereas FCS-induced [3H]thymidine incorporation into rat synchronized endothelial cells was unaffected by this agent. The dose of YC-1 required to cause inhibition of FCS-induced proliferation was similar to that necessary for the formation of cellular cyclic GMP (cGMP). Guanylate cyclase activity in soluble fractions of VSMCs was activated by YC-1 (1-100 microM), whereas cGMP-specific phosphodiesterase activity was unaffected by this compound. The anti-proliferative effect of YC-1 was mimicked by 8-bromo-cGMP, a membrane-permeable cGMP analogue, and was antagonized by KT 5823 (0.2 microM), a selective inhibitor of protein kinase G. The anti-proliferative effect of YC-1 was also antagonized by Methylene Blue (50 microM), a guanylate cyclase inhibitor, and was potentiated by 3-isobutyl-1-methylxanthine (500 microM), a phosphodiesterase inhibitor. These results verified that YC-1 is a direct soluble guanylate cyclase activator in A10 VSMCs, and the anti-proliferative effect of YC-1 is mediated by cGMP. YC-1 still inhibited FCS-induced DNA synthesis even when added 10-18 h after restimulation of the serum-deprived A10 VSMCs with 10% FCS. Flow cytometry in synchronized populations revealed an acute blockage of FCS-inducible cell-cycle progression at a point in the G1\/S-phase in YC-1 (100 microM)-treated cells. The inhibition of proliferation by YC-1 was demonstrated to be independent of cell damage, as documented by several criteria of cell viability. In conclusion, YC-1 reversibly and effectively inhibited the proliferation of VSMCs, suggesting that it has potential as a therapeutic agent in the prevention of vascular diseases.<\/jats:p>","DOI":"10.1042\/bj3060787","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:42:10Z","timestamp":1439242930000},"page":"787-792","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Mechanism of anti-proliferation caused by YC-1, an indazole derivative, in cultured rat A10 vascular smooth-muscle cells"],"prefix":"10.1042","volume":"306","author":[{"given":"S M","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Chang Gung Medical College, 259 Wen-Hwa 1st Road, Kwei-San, Tao-Yuan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z J","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Chang Gung Medical College, 259 Wen-Hwa 1st Road, Kwei-San, Tao-Yuan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J H","family":"Guh","sequence":"additional","affiliation":[{"name":"Pharmacological Institute, College of Medicine, National Taiwan University, Jen-Ai Road, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F Y","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, China Medical College, Taichung"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S C","family":"Kuo","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, China Medical College, Taichung"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","updated-by":[{"DOI":"10.1042\/bj3350191","type":"retraction","label":"Retraction","source":"retraction-watch","updated":{"date-parts":[[1998,10,1]],"date-time":"1998-10-01T00:00:00Z","timestamp":907200000000},"record-id":"1047"}],"container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/306\/3\/787\/615370\/bj3060787.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/306\/3\/787\/615370\/bj3060787.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T22:44:53Z","timestamp":1637707493000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/306\/3\/787\/30714\/Mechanism-of-anti-proliferation-caused-by-YC-1-an"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,3,15]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1995,3,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj3060787","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,3,15]]}}}