title: Gap junctions propagate opposite effects in normal and tumor testicular cells in response to cisplatin.
abstract: 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.
authors: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, People's Republic of China.
authors: Xiaoting
authors: X
authors: Hong
authors: Qin
authors: Q
authors: Wang
authors: Yan
authors: Y
authors: Yang
authors: Suping
authors: S
authors: Zheng
authors: Xuhui
authors: X
authors: Tong
authors: Suzhi
authors: S
authors: Zhang
authors: Liang
authors: L
authors: Tao
authors: Andrew L
authors: AL
authors: Harris
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology*; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D034622:RNA Interference; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D018031:Connexin 43; C119129:18alpha-glycyrrhetinic acid; D006034:Glycyrrhetinic Acid; D002945:Cisplatin