Gap junctions propagate opposite effects in normal and tumor testicular cells in response to cisplatin
| Autor: | Suping Zheng, Qin Wang, Xiaoting Hong, Xuhui Tong, Suzhi Zhang, Yan Yang, Andrew L. Harris, Liang Tao |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Cancer Research Cell Survival Blotting Western Antineoplastic Agents Cell Communication Biology Cell Line Mice Testicular Neoplasms Downregulation and upregulation Cell Line Tumor Testis medicine Bystander effect Animals Cytotoxicity Cisplatin Sertoli Cells Gap junction Gap Junctions Leydig Cells Cell biology Oncology Cell culture Connexin 43 Toxicity Glycyrrhetinic Acid RNA Interference Intracellular medicine.drug |
| Zdroj: | Cancer Letters. 317:165-171 |
| ISSN: | 0304-3835 |
| Popis: | Gap junctions propagate toxic effects among tumor cells during chemotherapy, but could also enhance killing of normal cells by the same mechanism. We show that the effect of gap junctional intercellular communication (GJIC) on cisplatin toxicity differs between normal and tumor testicular cells. Downregulation of GJIC by each of several different manipulations (no cell contact, pharmacological inhibition, siRNA suppression) decreased cisplatin cytoxicity in tumor cells but enhanced it in normal cells. Enhanced toxicity due to GJIC downregulation in normal cells correlated with increased DNA interstrand crosslinks. Thus, GJIC protects normal cells from cisplatin toxicity while enhancing it in tumor cells, suggesting that enhancement/maintenance of GJIC increases therapeutic efficacy while decreasing off-target toxicity. |
| Databáze: | OpenAIRE |
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