{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:09:57Z","timestamp":1791043797390,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,5,17]],"date-time":"2012-05-17T00:00:00Z","timestamp":1337212800000},"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":[[2012,6]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold>Endostatin (ES) is a c\u2010terminal proteolytic fragment of collagen XVIII with promising antitumour properties in several tumour models, including human glioblastoma. We hypothesized that this peptide could interact with plasma membrane ion channels and modulate their functions.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold>Using cell proliferation and migration assays, patch clamp and Western blot analysis, we studied the effects of ES on the proliferation and migration of human glioblastoma U87 cells, mediated by T\u2010type Ca<jats:sup>2+<\/jats:sup>channels.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold>Extracellular application of ES reversibly inhibited T\u2010type Ca<jats:sup>2+<\/jats:sup>channel currents (T\u2010currents) in U87 cells, whereas L\u2010type Ca<jats:sup>2+<\/jats:sup>currents were not affected. This inhibitory effect was associated with a hyperpolarizing shift in the voltage\u2010dependence of inactivation but was independent of G\u2010protein and protein tyrosine kinase\u2010mediated pathways. All three \u03b1<jats:sub>1<\/jats:sub>subunits of T\u2010type Ca<jats:sup>2+<\/jats:sup>channels (Ca<jats:sub>V<\/jats:sub>3), \u03b1<jats:sub>1G<\/jats:sub>(Ca<jats:sub>V<\/jats:sub>3.1), \u03b1<jats:sub>1H<\/jats:sub>(Ca<jats:sub>V<\/jats:sub>3.2) and \u03b1<jats:sub>1I<\/jats:sub>(Ca<jats:sub>V<\/jats:sub>3.3), were endogenously expressed in U87 cells. Using transfected HEK293 or CHO cells, we showed that only Ca<jats:sub>V<\/jats:sub>3.1 and Ca<jats:sub>V<\/jats:sub>3.2, but not Ca<jats:sub>V<\/jats:sub>3.3 or Ca<jats:sub>V<\/jats:sub>1.2 (L\u2010type), channel currents were significantly inhibited. More interestingly, ES inhibited the proliferation and migration of U87 cells in a dose\u2010dependent manner. Pretreatment of the cells with the specific T\u2010type Ca<jats:sup>2+<\/jats:sup>channel blocker mibefradil occluded these inhibitory effects of ES.<\/jats:p><jats:p><jats:bold>CONCLUSION AND IMPLICATIONS<\/jats:bold>This study provides the first evidence that the antitumour effects of ES on glioblastoma cells is through direct inhibition of T\u2010type Ca<jats:sup>2+<\/jats:sup>channels and gives new insights into the future development of a new class of antiglioblastoma agents that target the proliferation and migration of these cells.<\/jats:p><jats:p><jats:bold>LINKED ARTICLE<\/jats:bold>This article is commented on by Santoni<jats:italic>et\u2003al<\/jats:italic>., pp. 1244\u20131246 of this issue. To view this commentary visit<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/j.1476-5381.2012.01908.x\">http:\/\/dx.doi.org\/10.1111\/j.1476\u20105381.2012.01908.x<\/jats:ext-link><\/jats:p>","DOI":"10.1111\/j.1476-5381.2012.01852.x","type":"journal-article","created":{"date-parts":[[2012,1,10]],"date-time":"2012-01-10T13:41:28Z","timestamp":1326202888000},"page":"1247-1260","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Inhibition of T\u2010type Ca<sup>2+<\/sup>channels by endostatin attenuates human glioblastoma cell proliferation and 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