Glycolysis inhibition and its effect in doxorubicin resistance in neuroblastoma

Jonathan F. Bean, Yi Yong Qiu, Songtao Yu, Sandra Clark, Fei Chu*, Mary Beth Madonna

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Background/purpose 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 72 hours in normoxic conditions. A similar response was replicated in hypoxic conditions. Treatment with 3-bromopyruvate significantly decreased intracellular ATP and lactate levels. Conclusion Glycolysis inhibitors such as 3-bromopyruvate could prove to become an effective means by which chemotherapy resistance can be overcome in human neuroblastoma.

Original languageEnglish (US)
Pages (from-to)981-984
Number of pages4
JournalJournal of pediatric surgery
Volume49
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • 3-bromopyruvate
  • ATP
  • Doxorubicin
  • Glycolysis inhibition
  • Neuroblastoma

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

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