Systemic administration of 3-bromopyruvate reveals its interaction with serum proteins in a rat model

Rani Kunjithapatham, Jean Francois H. Geschwind, Pramod P. Rao, Tatiana N. Boronina, Robert N. Cole, Shanmugasundaram Ganapathy-Kanniappan

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Background: 3-bromopyruvate (3-BrPA) is a glycolytic inhibitor that affects cancer cells by targeting energy metabolism. Preclinical reports have established that a 1.75 mM dose of 3-BrPA is effective and sufficient to inhibit tumor growth when administered under a loco-regional approach (intraarterial and intratumoral). This loco-regional therapeutic dose was found to be nontoxic when given systemically as well. Yet, the mechanism underlying this lack of toxicity of 1.75 mM 3-BrPA during systemic delivery is unknown. Here, we investigated the mechanism associated with the lack of organ toxicity when 1.75 mM 3-BrPA was administered systemically using radiolabeled (14C)-3- BrPA in Sprague-Dawley rats. Findings. Data obtained from tissue-autoradiography of rats infused with 14C-3-BrPA showed strong 14C-signal in tissue sections of various organs except the brain corroborating that 3-BrPA does not cross the blood-brain barrier. Significantly, Hematoxylin & Eosin staining and apoptosis assay of tissue sections positive for 14C-signal showed no signs of toxicity or apoptosis. Convincingly, the 14C-signal observed in tissue-autoradiography emanates from 3-BrPA that is non-reactive or non-toxic, hence we further investigated whether the lack of toxicity is due to its interaction or alkylation with serum components. Analysis of serum proteins by 1D and 2D-gel electrophoretic autoradiography showed that 14C-BrPA selectively binds to peptides of molecular mass ∼50-60 kDa. Mass spectrometry data suggested that 14C-BrPA could interact with alpha1-antitrypsin and a peptide of albuminoid-family. Conclusion: Our data indicate that selective interaction of 3-BrPA with serum proteins could contribute to the apparent lack of tissue-toxicity at the indicated close when the drug is given systematically in Sprague-Dawley rats.

Original languageEnglish (US)
Article number277
JournalBMC Research Notes
Issue number1
StatePublished - 2013
Externally publishedYes


  • 2D gel electrophoresis
  • 3-bromopyruvate
  • Alpha1 antitrypsin
  • LC-MS/MS

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Systemic administration of 3-bromopyruvate reveals its interaction with serum proteins in a rat model'. Together they form a unique fingerprint.

Cite this