title: Glycolysis inhibition and its effect in doxorubicin resistance in neuroblastoma.
abstract: OBJECTIVE
  A common trait among cancers is the increased level of glycolysis despite adequate oxygen levels to support aerobic respiration. This has been shown repeatedly in different human malignancies. Glycolysis inhibitors, especially 3-bromopyruvate, have been shown to be effective chemotherapeutic agents. The effect of glycolysis inhibition upon chemotherapy resistance is relatively unknown.
  
  
  METHODS
  Wild-type and doxorubicin-resistant lines of neuroblastoma (SK-N-SH and SK-N-Be(2)C) were used in this study. Using an MTT assay, the IC50 of 3-BrPA was determined. Subsequently, doxorubicin-resistant cell lines were treated with 3-bromopyruvate, doxorubicin, and 3-bromopyruvate with doxorubicin. Additionally, a luminescence ATP detection assay was used to measure intracellular ATP levels, and a lactate assay was used to determine intracellular lactate levels. All experiments were repeated in hypoxic conditions.
  
  
  RESULTS
  Treatment with 3-bromopyruvate and doxorubicin significantly decreased the mean cell viabilities at 24, 48, and 72hours in normoxic conditions. A similar response was replicated in hypoxic conditions. Treatment with 3-bromopyruvate significantly decreased intracellular ATP and lactate levels.
  
  
  CONCLUSIONS
  Glycolysis inhibitors such as 3-bromopyruvate could prove to become an effective means by which chemotherapy resistance can be overcome in human neuroblastoma.
authors.affiliation: Department of Pediatric Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611; Cancer Biology and Epigenetics, Children's Hospital of Chicago Research Center, Chicago, IL 60641.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Bean
authors.affiliation: Cancer Biology and Epigenetics, Children's Hospital of Chicago Research Center, Chicago, IL 60641.
authors.forename: Yi-Yong
authors.initials: YY
authors.lastname: Qiu
authors.affiliation: Cancer Biology and Epigenetics, Children's Hospital of Chicago Research Center, Chicago, IL 60641.
authors.forename: Songtao
authors.initials: S
authors.lastname: Yu
authors.affiliation: Cancer Biology and Epigenetics, Children's Hospital of Chicago Research Center, Chicago, IL 60641.
authors.forename: Sandra
authors.initials: S
authors.lastname: Clark
authors.affiliation: Cancer Biology and Epigenetics, Children's Hospital of Chicago Research Center, Chicago, IL 60641. Electronic address: fchu@luriechildrens.org.
authors.forename: Fei
authors.initials: F
authors.lastname: Chu
authors.affiliation: Department of Pediatric Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611; Cancer Biology and Epigenetics, Children's Hospital of Chicago Research Center, Chicago, IL 60641. Electronic address: mmadonna@luriechildrens.org.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Madonna
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival; D004317:Doxorubicin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D000255:Adenosine Triphosphate
keywords: 3-bromopyruvate; ATP; Doxorubicin; Glycolysis inhibition; Neuroblastoma