Development of a dichloroacetic acid-hemoglobin conjugate as a potential targeted anti-cancer therapeutic

Biotechnol Bioeng. 2011 Jun;108(6):1413-20. doi: 10.1002/bit.23071. Epub 2011 Feb 18.


This work focuses on conjugating the anti-cancer drug dichloroacetic acid (DCA) to the monocyte/macrophage targeting protein hemoglobin (Hb). The DCA-Hb conjugate carries approximately 12 DCA molecules per Hb tetramer, and binds to haptoglobin (Hp) forming stable DCA-Hb-Hp complexes, in a similar manner to unmodified Hb. The results of this study show that DCA-Hb-Hp is taken up by the monocytic cancer cell line THP-1, where it depolarizes the mitochondrial membrane potential, thereby inhibiting cancerous cell growth at a comparable level to free DCA. Taken together, the results of this study show promise for the use of the DCA-Hb conjugate as a potential therapeutic to treat monocytic leukemia.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Dichloroacetic Acid / chemistry*
  • Dichloroacetic Acid / pharmacokinetics
  • Dichloroacetic Acid / pharmacology
  • Drug Delivery Systems*
  • Haptoglobins / metabolism*
  • Hemoglobin A / chemistry*
  • Hemoglobin A / pharmacokinetics
  • Hemoglobin A / pharmacology
  • Humans
  • Macrophages / metabolism
  • Monocytes / metabolism
  • Neoplasms / drug therapy*
  • Protein Binding


  • Antineoplastic Agents
  • Haptoglobins
  • Hemoglobin A
  • Dichloroacetic Acid