{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T01:10:17Z","timestamp":1784855417192,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T00:00:00Z","timestamp":1384387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Follicular lymphoma is the second most common non\u2010<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>odgkin's lymphoma and, despite the introduction of rituximab for its treatment, this disease is still considered incurable. Besides genetic alterations involving <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>cl\u20102, <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>cl\u20106 or c\u2010<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>yc, follicular lymphoma cells often display altered <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>\u2010cell receptor signalling pathways including overactive <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PI3K\/Akt<\/jats:styled-content> systems.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The effect of enzastaurin, an inhibitor of PKC, was evaluated both <jats:italic>in vitro<\/jats:italic> on follicular lymphoma cell lines and <jats:italic>in vivo<\/jats:italic> on a xenograft murine model. Using pharmacological inhibitors and <jats:styled-content style=\"fixed-case\"><jats:roman>siRNA<\/jats:roman><\/jats:styled-content> transfection, we determined the different signalling pathways after enzastaurin treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Enzastaurin inhibited the serine\u2010threonine kinase <jats:styled-content style=\"fixed-case\">p90RSK<\/jats:styled-content> which has downstream effects on <jats:styled-content style=\"fixed-case\">GSK3<\/jats:styled-content>\u03b2. Bad and <jats:styled-content style=\"fixed-case\">p70S6K<\/jats:styled-content>. These signalling proteins control follicular lymphoma cell survival and apoptosis; which accounted for the inhibition by enzastaurin of cell survival and its induction of apoptosis of follicular lymphoma cell lines <jats:italic>in vitro.<\/jats:italic> Importantly, these results were replicated <jats:italic>in vivo<\/jats:italic> where enzastaurin inhibited the growth of follicular lymphoma xenografts in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>The targeting of <jats:styled-content style=\"fixed-case\">p90RSK<\/jats:styled-content> by enzastaurin represents a new therapeutic option for the treatment of follicular lymphoma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12351","type":"journal-article","created":{"date-parts":[[2013,8,29]],"date-time":"2013-08-29T02:12:48Z","timestamp":1377742368000},"page":"1374-1383","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The serine\u2010threonine kinase p90RSK is a new target of enzastaurin in follicular lymphoma cells"],"prefix":"10.1111","volume":"170","author":[{"given":"S","family":"Kheirallah","sequence":"first","affiliation":[{"name":"INSERM UMR1037\u2010Centre de Recherche en Canc\u00e9rologie de Toulouse  Toulouse France"},{"name":"Universit\u00e9 Toulouse III Paul\u2010Sabatier  Toulouse France"},{"name":"ERL 5294 CNRS, BP3028, H\u00f4pital Purpan  Toulouse France"},{"name":"Institut Carnot Lymphome\u2010CALYM  Toulouse France"},{"name":"Laboratoire d'Excellence Toulouse Cancer\u2010TOUCAN  Toulouse 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