{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T08:21:23Z","timestamp":1761380483131,"version":"build-2065373602"},"reference-count":0,"publisher":"Bentham Science Publishers Ltd.","issue":"3","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["AIAAMC"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>The human mast cell line HMC-1560,816 carries activating mutations in the proto-oncogene of c-kit that cause\nautophosphorylation and permanent c-kit receptor activation. The compound CCT129202 is a new and selective inhibitor\nof Aurora kinase A and B that decreases the viability of a variety of human tumor cell lines. The effect of Aurora kinase\ninhibition was assessed in the HMC-1560,816 line in order to find a suitable tool for mastocytosis treatment. CCT129202\ntreatment induces a significant decrease in cell viability in HMC-1560,816 cells after 48 hours of treatment. Moreover,\ncaspase-3 and caspase-8 activation was induced after incubation of HMC-1560,816 cells in the presence of CCT129202. It\nhas been demonstrated that Protein Kinase C (PKC) plays a crucial role in mast cell activation as well as cell migration,\nadhesion and apoptotic cell death. Co-treatment of Ca2+-independent PKCs (&amp;#948; &amp;#949; and &amp;#952;) inhibitor GF109203X with\nCCT129202, reduces caspase-3 activation which controls cell levels. In contrast, Go6976, an inhibitor of Ca2+-dependent\nPKCs, increases caspase-3 activation. Oppositely, GF109203X does not modify CCT129202-induced apoptosis through\nthe caspase-8 pathway whereas Go6976 treatment abolishes the increase on caspase-8 activity due to CCT129202. This\nimplies that Ca2+-independent PKC isoforms seems to be related with CCT129202-induced apoptosis through the caspase-\n3 pathway, whereas Ca2+-dependent PKC isoforms are related with the CCT129202 effect on the caspase-8 pathway. Interestingly,\nCCT129202 cytotoxic effect remains even though Ca2+-dependent PKCs are inhibited, which shows that the\nAurora kinase inhibitor effect is acting through the caspase-3 pathway. On the other hand, Ca2+-independent PKCs inhibition\ndoes not affect the final apoptotic CCT129202 effect because this seems to be mediated by the caspase-8 pathway.\nMoreover, CCT129202 does not affect PKC&amp;#948; and Ca2+-dependent PKC translocation, which indicates that PKC translocation\npivots on its activation. This demonstrates that Aurora kinase inhibition is not related to this process. Finally, when\nPKC is silenced in HMC-1560,816 cells, the effect of CCT129202 on the caspase-3 pathway disappears, which indicates that\nthe CCT129202 effect is clearly PKC-dependent.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2174\/18715230113129990002","type":"journal-article","created":{"date-parts":[[2013,7,9]],"date-time":"2013-07-09T14:39:09Z","timestamp":1373380749000},"page":"265-276","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Protein Kinase C Modulates Aurora-kinase Inhibition Induced by CCT129202 in HMC-1560,816 Cell Line"],"prefix":"10.2174","volume":"12","author":[{"given":"Araceli","family":"Tobio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amparo","family":"Alfonso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Fernandez-Araujo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Alonso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis M.","family":"Botana","sequence":"additional","affiliation":[{"name":"Universidad de Santiago de Compostela. Dept. Farmacologia, Facultad de Veterinaria, 27002 Lugo, Spain.,Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","container-title":["Anti-Inflammatory &amp; Anti-Allergy Agents in Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/18715230113129990002","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/112675\/article","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/18715230113129990002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T08:17:12Z","timestamp":1761380232000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eurekaselect.com\/112675\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/18715230113129990002","relation":{},"ISSN":["1871-5230"],"issn-type":[{"type":"print","value":"1871-5230"}],"subject":[],"published":{"date-parts":[[2013,12]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Double blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-06-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}