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The aim of this study is to investigate whether curcumin modulates cell apoptosis through the alternation of the connexin 43 (Cx43) protein level in TMZ-resistant GBM.\u00a0Overexpression of Cx43, but not ATP-binding cassette transporters (ABC transporters), was observed (approximately 2.2-fold) in TMZ-resistant GBM cells compared to the Cx43 levels in parental GBM cells. Furthermore, at a concentration of 10[Formula: see text][Formula: see text]M, curcumin significantly reduced Cx43 protein expression by about 40%. In addition, curcumin did not affect the expression of other connexins like Cx26 or epithelial-to-mesenchymal transition (EMT) proteins such as [Formula: see text]-catenin or [Formula: see text]E-catenin. Curcumin treatment led to an increase in TMZ-induced cell apoptosis from 4% to 8%. Importantly, it did not affect the mRNA expression level of Cx43. Concomitant treatment with the translation inhibitor cycloheximide (CHX) exerted additional effects on Cx43 degradation. Treatment with the autophagy inhibitor 3-MA (methyladenine) did not affect the curcumin-induced Cx43 degradation. Interestingly, treatment with the proteasome inhibitor MG132 (carbobenzoxy-Leu-Leu-leucinal) significantly negated the curcumin-induced Cx43 degradation, which suggests that curcumin-induced Cx43 degradation occurs through the ubiquitin-proteasome pathway.<\/jats:p>","DOI":"10.1142\/s0192415x19500344","type":"journal-article","created":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T06:46:26Z","timestamp":1555051586000},"page":"657-674","source":"Crossref","is-referenced-by-count":22,"title":["Curcumin Promotes Connexin 43 Degradation and Temozolomide-Induced Apoptosis in Glioblastoma Cells"],"prefix":"10.1142","volume":"47","author":[{"given":"Bor-Ren","family":"Huang","sequence":"first","affiliation":[{"name":"Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan"},{"name":"Department of Neurosurgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chon-Haw","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Neurology, China Medical University Hospital, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Chuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, College of Life Science, National Chung Hsing University, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzong-Der","family":"Way","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Yie","family":"Kao","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, College of Life Science, National Chung Hsing University, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Shu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiao-Yun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng-Wei","family":"Lai","sequence":"additional","affiliation":[{"name":"Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dah-Yuu","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan"},{"name":"Department of Photonics and Communication Engineering, Asia University, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"219","published-online":{"date-parts":[[2019,5,23]]},"reference":[{"key":"S0192415X19500344BIB001","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.105"},{"key":"S0192415X19500344BIB002","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nou215"},{"key":"S0192415X19500344BIB003","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e11-10-0844"},{"key":"S0192415X19500344BIB004","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2004.08.002"},{"key":"S0192415X19500344BIB005","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201490784"},{"key":"S0192415X19500344BIB006","first-page":"CD007415","author":"Hart M.G.","year":"2013","journal-title":"Cochrane Database Syst. 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