title: Chlorogenic acid enhances the effects of 5-fluorouracil in human hepatocellular carcinoma cells through the inhibition of extracellular signal-regulated kinases.
abstract: There is an urgent need to search for novel chemosensitizers in the field of cancer therapy. Chlorogenic acid (CGA), a type of polyphenol present in the diet, has many biological activities. The present study is designed to explore the influence of CGA on the effects of 5-fluorouracil (5-FU) on human hepatocellular carcinoma cells (HepG2 and Hep3B). Treatment with 5-FU induced the inhibition of hepatocellular carcinoma cells' proliferation, and the combined treatment with CGA enhanced this inhibition. 5-FU also increased the production of reactive oxygen species (ROS). The combination of 5-FU and CGA led to a more prominent production of ROS and significantly inactivated ERK1/2, although CGA and 5-FU exerted no significant changes when used alone. A previous report has shown that ROS are upstream mediators that inactivate ERK in hepatocellular carcinoma cells. Combined with our results, this indicates that the combination of 5-FU and CGA leads to the inactivation of ERK through the overproduction of ROS. This mediates the enhancement of 5-FU-induced inhibition of hepatocellular carcinoma cells' proliferation, that is, CGA sensitizes hepatocellular carcinoma cells to 5-FU treatment by the suppression of ERK activation through the overproduction of ROS. CGA has shown potential as a chemosensitizer of 5-FU chemotherapy in hepatocellular carcinoma.
authors.affiliation: Departments of aGastroenterology bGeneral Surgery, The Second Affiliated Hospital cDepartment of Genetics and Molecular Biology, School of Medicine, Xi'an Jiaotong University dDepartment of Gastroenterology, Xi'an Central Hospital, Xi'an, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yan
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Han
authors.forename: Ni
authors.initials: N
authors.lastname: Hou
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002726:Chlorogenic Acid / Q000494:pharmacology*; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D002726:Chlorogenic Acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D005472:Fluorouracil