title: FX11 inhibits aerobic glycolysis and growth of neuroblastoma cells.
abstract: The MYC family of proteins promotes neuroblastoma tumorigenesis at least in part through the induction of aerobic glycolysis by promoting the transcription of key glycolytic enzymes, such as LDHA. FX11 is a selective inhibitor of LDHA that has demonstrated preclinical efficacy in adult cancers. Herein, we hypothesized that FX11 would inhibit aerobic glycolysis and block growth of neuroblastoma cells.
  
  
  
  We surveyed 3 MYCN-single copy and 5 MYCN-amplified neuroblastoma cell lines to correlate C-MYC/N-MYC protein levels with LDHA expression. Cell viability was measured with FX11 using a tetrazolium-based assay. Cell cycle analysis using propidium iodide with flow cytometry was performed to evaluate for growth arrest. Immunoblotting demonstrated PARP and Caspase 3 cleavage as evidence of apoptosis.
  
  
  
  LDHA is frequently expressed in both MYCN--amplified and MYCN-single copy cell lines. N-MYC and C-MYC protein levels did not correlate with LDHA protein expression. FX11 inhibits aerobic glycolysis and growth in three MYCN-amplified and one MYCN-single copy neuroblastoma cell lines. FX11 induces modest G1 cell cycle arrest with selective induction of apoptosis.
  
  
  
  Small molecule LDHA inhibition is capable of blocking aerobic glycolysis and growth of neuroblastoma cell lines in vitro and merits further in vivo evaluation of its preclinical efficacy in neuroblastomas.
authors.affiliation: Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Rellinger
authors.affiliation: Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Craig
authors.affiliation: Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Alvarez
authors.affiliation: Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Haley L
authors.initials: HL
authors.lastname: Dusek
authors.affiliation: Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Kwang W
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN; Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN. Electronic address: dai.chung@vanderbilt.edu.
authors.forename: Dai H
authors.initials: DH
authors.lastname: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D000071447:N-Myc Proto-Oncogene Protein / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism
chemical_list: C547455:3-dihydroxy-6-methyl-7-(phenylmethyl)-4-propylnaphthalene-1-carboxylic acid; D000071447:N-Myc Proto-Oncogene Protein; D009281:Naphthalenes; D016271:Proto-Oncogene Proteins c-myc