title: Total flavonoids of litsea coreana enhance the cytotoxicity of oxaliplatin by increasing gap junction intercellular communication.
abstract: Oxaliplatin is widely used in the treatment of variety of cancers, including cancer of the testis and colorectum. Gap junctions (GJs) can amplify the cytotoxicity of antinoeoplastic drugs through the bystander effect in different cancer cells. In this study, we demonstrate that total flavonoids of litsea coreana (TFLC), one extract from the dried leaves of litsea coreana leve, increase the cytotoxicity of oxaliplatin in mouse testicular cancer I-10 cells. We found that cell survival was substantially decreased only when functional GJs formed in I-10 cells. TFLC increased oxaliplatin cytotoxity (inducing cell death and apoptosis) by enhancing gap junction intercellular communication (GJIC) through elevated Cx43 protein expression. Furthermore, apoptosis-related protein (Bax, Bcl-2, caspase-3/9) results showed that the Bax/Bcl-2 ratio and activated caspase-3/9 increased when TFLC was used compared with treatment with oxaliplatin alone, which suggests that the mechanism of increased oxaliplatin-induced apoptosis was through the mitochondrial pathway. These results demonstrate that TFLC can enhance the cytotoxicity of oxaliplatin, and that these processes may be regulated in testicular tumor cells through GJ-mediated regulation of tumor cell apoptosis.
authors.affiliation: Department of Pharmacy, Bengbu Medical College.
authors.forename: Bin-bin
authors.initials: BB
authors.lastname: Yu
authors.forename: Shu-ying
authors.initials: SY
authors.lastname: Dong
authors.forename: Mei-ling
authors.initials: ML
authors.lastname: Yu
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Jiang
authors.forename: Jie
authors.initials: J
authors.lastname: Ji
authors.forename: Xu-hui
authors.initials: XH
authors.lastname: Tong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018031:Connexin 43 / Q000378:metabolism; D004357:Drug Synergism; D005419:Flavonoids / Q000494:pharmacology*; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D032862:Litsea; D051379:Mice; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494827:Bax protein, mouse; D018031:Connexin 43; D005419:Flavonoids; D009944:Organoplatinum Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000077150:Oxaliplatin; D053148:Caspase 3; D053453:Caspase 9