{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T07:15:23Z","timestamp":1777619723514,"version":"3.51.4"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,9,4]],"date-time":"2017-09-04T00:00:00Z","timestamp":1504483200000},"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":[[2018,3]]},"abstract":"<jats:sec><jats:label\/><jats:p>Extracellular nucleotides can regulate cell proliferation in both normal and tumorigenic tissues. Here, we studied how extracellular nucleotides regulate the proliferation of ZL55 cells, a mesothelioma\u2010derived cell line obtained from bioptic samples of asbestos\u2010exposed patients. ADP and 2\u2010MeS\u2010ADP inhibited ZL55 cell proliferation, whereas ATP, UTP, and UDP were inactive. The nucleotide potency profile and the blockade of the ADP\u2010mediated inhibitory effect by the phospholipase C inhibitor U\u201073122 suggest that P2Y1 receptor controls ZL55 cell proliferation. The activation of P2Y1 receptor by ADP leads to activation of intracellular transduction pathways involving [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, PKC\u2010\u03b4\/PKC\u2010\u03b1, and MAPKs, ERK1\/2 and JNK1\/2. Cell treatment with ADP or 2\u2010MeS\u2010ADP also provokes the activation of p53, causing an accumulation of the G1 cyclin\u2010dependent kinase inhibitors p21<jats:sup>WAF1<\/jats:sup>and p27<jats:sup>Kip<\/jats:sup>. Inhibition of ZL55 cell proliferation by ADP was completely reversed by inhibiting MEK1\/2, or JNK1\/2, or PKC\u2010\u03b4, and PKC\u2010\u03b1. Through the inhibition of ADP\u2010activated transductional kinases it was found that PKC\u2010\u03b4 was responsible for JNK1\/2 activation. JNK1\/2 has a role in transcriptional up\u2010regulation of p53, p21<jats:sup>WAF1\/CIP1<\/jats:sup>, and p27<jats:sup>kip1<\/jats:sup>. Conversely, the ADP\u2010activated PKC\u2010\u03b1 provoked ERK1\/2 phosphorylation. ERK1\/2 increased p53 stabilization, required to G1 arrest of ZL55 cells. Concluding, the importance of the study is twofold: first, results shed light on the mechanism of cell cycle inhibition by ADP; second, results suggest that extracellular ADP may inhibit mesothelioma progression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.26128","type":"journal-article","created":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T12:52:40Z","timestamp":1501851160000},"page":"2526-2536","source":"Crossref","is-referenced-by-count":9,"title":["Inhibition of ZL55 cell proliferation by ADP via PKC\u2010dependent signalling pathway"],"prefix":"10.1002","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2822-9929","authenticated-orcid":false,"given":"Antonella","family":"Muscella","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (Di.S.Te.B.A.) Universita\u2019 del Salento Lecce Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca G.","family":"Cossa","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (Di.S.Te.B.A.) Universita\u2019 del Salento Lecce Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Vetrugno","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (Di.S.Te.B.A.) Universita\u2019 del Salento Lecce Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Antonaci","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (Di.S.Te.B.A.) Universita\u2019 del Salento Lecce Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santo","family":"Marsigliante","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (Di.S.Te.B.A.) Universita\u2019 del Salento Lecce Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,9,4]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400885"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119603"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-013-9372-5"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-210526"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.11.086678"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(02)00196-3"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2004.10.013"},{"key":"e_1_2_5_9_1","first-page":"4450","article-title":"The c\u2010Jun NH(2)\u2010terminal protein kinase\/AP\u20101 pathway is required for efficient apoptosis induced by vinblastine","volume":"61","author":"Fan M.","year":"2001","journal-title":"Cancer Research"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.17.2658"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.1.506"},{"issue":"8","key":"e_1_2_5_12_1","first-page":"639","article-title":"The role of the cyclin\u2010dependent kinase inhibitor p21 in apoptosis","volume":"1","author":"Gartel A. 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