title: Combination of baicalein and 10-hydroxy camptothecin exerts remarkable synergetic anti-cancer effects.
abstract: BACKGROUND
  10-Hydroxy camptothecin (HCPT), a naturally occurring alkaloid, is a clinical drug for cancer chemotherapy. Baicalein (BA) is a flavonoid extracted from the root of Scutellaria baicalensis. The synergistic anti-cancer effect of BA and HCPT has not been reported.
  
  
  OBJECTIVE
  To explore whether and how BA enhances the anti-cancer effect of HCPT in BGC823 cells.
  
  
  METHODS
  Cell viability was measured by MTT assay. Apoptosis and cell cycle were analyzed through flow cytometry and western blotting analysis. DNA damage was determined by a comet assay. The activity of topoisomerase I (Topo I) was detected by the plasmid DNA relaxation assay. The synergistic anti-cancer effect of BA and HCPT in vivo was tested by BGC823 xenografted tumor model.
  
  
  RESULTS
  BA at non-toxic doses prominently enhanced the anti-cancer activities of HCPT in BGC823, MCF7 and SMMC7721 cells. Combination treatment of BA and HCPT induced BGC823 cells apoptosis mainly via intrinsic rather than extrinsic pathways, and preferentially arresting cell cycle in G1 and G2 phases with the aid of p21. Of note, p53, the upstream regulator of cell apoptosis and cycle, was increased by 5 folds in combination group. It helped to further trigger DNA damage and inhibit Topo I catalytic activity after combination treatment of BA and HCPT. Moreover, the BGC823 xenografted tumor growth rate in nude mice was repressed in a greater degree (P< 0.01) in the combinational group than the single-drug group.
  
  
  CONCLUSIONS
  HCPT and BA, a new and effective combination therapy, synergistically target Topo I and up-regulate p53 to induce cell apoptosis and cell cycle arrest.
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian, 116024 China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Tang
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian, 116024 China.
authors.forename: Fangling
authors.initials: F
authors.lastname: Ji
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian, 116024 China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Sun
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian, 116024 China.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian, 116024 China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, Dalian, 116044 China.
authors.forename: Lianying
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, Dalian, 116044 China. Electronic address: liy76@yahoo.com.
authors.forename: Yachen
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian, 116024 China; School of Food and Environmental Science and Technology, Dalian University of Technology, Panjin, 124221 China. Electronic address: biosci@dlut.edu.cn.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Bao
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000494:pharmacology* / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004338:Drug Combinations; D004357:Drug Synergism; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D031364:Scutellaria baicalensis / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D044950:Flavanones; D010936:Plant Extracts; C006680:baicalein; D002166:Camptothecin
keywords: 10-hydroxy camptothecin; Anti-cancer; Apoptosis; Baicalein; Topoisomerase I; p53