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

Seishiro CHIKAZAWA; Yasunori KITAHARA; Erika ANDO; Yasutomo HORI; Fumio HOSHI; Kazutaka KANAI; Naoyuki ITO; Seiichi HIGUCHI

doi:10.1292/jvms.13-0319

Internal Medicine

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

Seishiro CHIKAZAWA, Yasunori KITAHARA, Erika ANDO, Yasutomo HORI, Fumio HOSHI, Kazutaka KANAI, Naoyuki ITO, Seiichi HIGUCHI

Author information

Seishiro CHIKAZAWA
Department of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University, 23–35–1 Higashi, Towada, Aomori 034–8628, Japan
Yasunori KITAHARA
Department of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University, 23–35–1 Higashi, Towada, Aomori 034–8628, Japan
Erika ANDO
Department of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University, 23–35–1 Higashi, Towada, Aomori 034–8628, Japan
Yasutomo HORI
Department of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University, 23–35–1 Higashi, Towada, Aomori 034–8628, Japan
Fumio HOSHI
Department of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University, 23–35–1 Higashi, Towada, Aomori 034–8628, Japan
Kazutaka KANAI
Department of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University, 23–35–1 Higashi, Towada, Aomori 034–8628, Japan
Naoyuki ITO
Department of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University, 23–35–1 Higashi, Towada, Aomori 034–8628, Japan
Seiichi HIGUCHI
Department of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University, 23–35–1 Higashi, Towada, Aomori 034–8628, Japan

Keywords: artesunate, DH82, dihydroartemisinin, erythrophagocytosis

JOURNAL FREE ACCESS

2014 Volume 76 Issue 2 Pages 249-253

DOI https://doi.org/10.1292/jvms.13-0319

Browse “Advance online publication” version

Details

Abstract

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.

Corresponding author

Register with J-STAGE for free!