Connexin 43 (cx43) enhances chemotherapy-induced apoptosis in human glioblastoma cells.
Stable re-expression of connexin 43 (cx43) in human glioblastoma suppresses transformation and tumorigenicity. The present study was designed to examine the role of cx43 in chemotherapy-induced apoptosis. Expression of cx43 in human glioblastoma cells significantly increased sensitivity to several common chemotherapeutic agents, including etoposide, paclitaxel (Taxol) and doxorubicin, compared with control-transfected cells. The increased sensitivity to chemotherapeutic agents resulted from apoptosis as evidenced by Hoechst dye staining, TUNEL assay and annexin V assay. These cx43-mediated effects were coupled with decreased expression of the specific apoptosis inhibitor bcl-2. Over-expression of bcl-2 in cx43-transfected cells partially confers the resistance to apoptosis induced by etoposide, suggesting that the cx43-mediated apoptosis to chemotherapeutic agents is regulated in part through the down-regulation of bcl-2 expression. Furthermore, the cx43-mediated apoptosis in response to chemotherapeutic drugs may not be linked to increased gap junctional communication in cx43-transfected cells. Our results demonstrate a new role of cx43 in the mediation of apoptosis during chemotherapy.
Division of Research, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA 30322, USA. rphuang@yahoo.com
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Hossain
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Gano
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D018031:Connexin 43 / Q000235:genetics / Q000494:pharmacology*; D004347:Drug Interactions; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D016195:G2 Phase / Q000187:drug effects; D017629:Gap Junctions / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007546:Isoquinolines; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018031:Connexin 43; D005456:Fluorescent Dyes; D007546:Isoquinolines; D019253:Proto-Oncogene Proteins c-bcl-2; D005047:Etoposide; C017475:lucifer yellow