title: A Mechanism for the Temporal Potentiation of Genipin to the Cytotoxicity of Cisplatin in Colon Cancer Cells.
abstract: OBJECTIVE
  To investigate the potentiation effect of Genipin to Cisplatin induced cell senescence in HCT-116 colon cancer cells in vitro.
  
  
  METHODS
  Cell viability was estimated by Propidium iodide and Hoechst 3342, reactive oxygen species (ROS) with DHE, mitochondrial membrane potential (MMP) with JC-1 MMP assay Kit and electron current production with microbial fuel cells (MFC).
  
  
  RESULTS
  Genipin inhibited the UCP2 mediated anti-oxidative proton leak significantly promoted the Cisplatin induced ROS and subsequent cell death, which was similar to that of UCP2-siRNA. Cells treated with Cisplatin alone or combined with Genipin, ROS negatively, while MMP positively correlated with cell viability. Cisplatin induced ROS was significantly decreased by detouring electrons to MFC, or increased by Genipin combined treatment. Compensatory effects of UCP2 up-regulation with time against Genipin treatment were suggested. Shorter the Genipin treatment before Cisplatin better promoted the Cisplatin induced ROS and subsequent cell death.
  
  
  CONCLUSIONS
  The interaction of leaked electron with Cisplatin was important during ROS generation. Inhibition of UCP2-mediated proton leak with Genipin potentiated the cytotoxicity of Cisplatin. Owing to the compensatory effects against Genipin, shorter Genipin treatment before Cisplatin was recommended in order to achieve better potentiation effect.
authors.affiliation: 1. Department of Gastroenterology, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong,China 518100.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Wang
authors.affiliation: 2. Program of Food Science and Technology, Division of Science and Technology, BNU-HKBU United International College, 28 Jinfeng Road, Tangjiawan, Zhuhai, Guangdong, China 519085.
authors.forename: K C
authors.initials: KC
authors.lastname: MoYung
authors.affiliation: 2. Program of Food Science and Technology, Division of Science and Technology, BNU-HKBU United International College, 28 Jinfeng Road, Tangjiawan, Zhuhai, Guangdong, China 519085.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Zhao
authors.affiliation: 2. Program of Food Science and Technology, Division of Science and Technology, BNU-HKBU United International College, 28 Jinfeng Road, Tangjiawan, Zhuhai, Guangdong, China 519085.
authors.forename: Karen
authors.initials: K
authors.lastname: Poon
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001674:Bioelectric Energy Sources; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004357:Drug Synergism; D045325:HCT116 Cells; D006801:Humans; D039823:Iridoids / Q000008:administration & dosage*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D039823:Iridoids; D017382:Reactive Oxygen Species; C007834:genipin; D002945:Cisplatin
keywords: Cisplatin; Genipin; cell electric current; cytotoxicity; mitochondrial membrane potential; reactive oxygen species