Erythrophagocytosis Enhances Heme-Dependent Cytotoxicity of Antimalarial Drugs in Canine Histiocytic Sarcoma Cell Line DH82

Antimalarial drugs, dihydroartemisinin (DHA) and artesunate (ATS), exhibit iron-dependent cytotoxicity in tumor cells. We hypothesized that erythrophagocytic uptake of heme-iron enhances the cytotoxicity of DHA and ATS. Erythrophagocytic (EP) treatment of the canine histiocytic sarcoma cell line DH8...

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Detalles Bibliográficos
Autores principales: CHIKAZAWA, Seishiro, KITAHARA, Yasunori, ANDO, Erika, HORI, Yasutomo, HOSHI, Fumio, KANAI, Kazutaka, ITO, Naoyuki, HIGUCHI, Seiichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Japanese Society of Veterinary Science 2013
Materias:
Internal Medicine
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982809/
https://www.ncbi.nlm.nih.gov/pubmed/24065080
http://dx.doi.org/10.1292/jvms.13-0319
Descripción
Sumario:Antimalarial drugs, dihydroartemisinin (DHA) and artesunate (ATS), exhibit iron-dependent cytotoxicity in tumor cells. We hypothesized that erythrophagocytic uptake of heme-iron enhances the cytotoxicity of DHA and ATS. Erythrophagocytic (EP) treatment of the canine histiocytic sarcoma cell line DH82 markedly increased the cytotoxicity of DHA and ATS compared to controls. Succinyl acetone, an inhibitor of intracellular heme synthesis, decreased the cytotoxicity of DHA and ATS in normal cells, but this change was not observed in EP cells. These results suggest that exogenous heme derived from erythrocytes can enhance the cytotoxicity of DHA and ATS. Furthermore, our study suggests that heme could be a novel component of tumor treatment in veterinary medicine.

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