title: Citrate induces apoptotic cell death: a promising way to treat gastric carcinoma?
abstract: Gastric carcinoma is frequent, particularly in China, and therapy is often inefficient. Because cancer cells are partly or mainly dependent on glycolysis to generate adenosine triphosphate ATP (Warburg effect) and/or to produce precursors (of lipid, nucleotides, etc.) for building new cells, any inhibition of glycolysis may slow down the cell proliferation and/or may kill cells. The antitumor effect of citrate, an anti-glycolytic agent inhibiting phosphofructokinase (PFK) was tested on two human gastric carcinoma cell lines.
  
  
  METHODS
  Cell viability and morphology were assessed after 24-72 h exposure to citrate (5, 10, 220 mM). Apoptosis was assessed by annexin V-FITC/PI staining and Western immunobloting.
  
  
  RESULTS
  A 3-day continuous exposure to citrate led to near destruction of the cell population in both cell lines, apoptotic cell death occurred through the mitochondrial pathway in a dose- and time-dependent manner, associated with the reduction of the anti-apoptotic Mcl-1 protein in both lines.
  
  
  CONCLUSIONS
  Citrate demonstrates strong cytotoxic activity against two gastric cancer lines, leading to an early diminution of expression of Mcl-1 and to massive apoptotic cell death involving the mitochondrial pathway.
authors.affiliation: Department of Thoracic Surgery, CHU de Caen, Avenue de la Côte de Nacre, 14000 Caen, France.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Lu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Haitian
authors.initials: H
authors.lastname: Zhang
authors.forename: Jiao
authors.initials: J
authors.lastname: Lan
authors.forename: Guangwu
authors.initials: G
authors.lastname: Huang
authors.forename: Emilie
authors.initials: E
authors.lastname: Varin
authors.forename: Hubert
authors.initials: H
authors.lastname: Lincet
authors.forename: Laurent
authors.initials: L
authors.lastname: Poulain
authors.forename: Philippe
authors.initials: P
authors.lastname: Icard
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D053144:Cell Nucleus Shape / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D019343:Citric Acid / Q000494:pharmacology* / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D019343:Citric Acid