title: Development of a dichloroacetic acid-hemoglobin conjugate as a potential targeted anti-cancer therapeutic.
abstract: 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.
authors.affiliation: William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Andre F
authors.initials: AF
authors.lastname: Palmer
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003999:Dichloroacetic Acid / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D006242:Haptoglobins / Q000378:metabolism*; D006441:Hemoglobin A / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy*; D011485:Protein Binding
chemical_list: D000970:Antineoplastic Agents; D006242:Haptoglobins; D006441:Hemoglobin A; D003999:Dichloroacetic Acid