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 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.
Department of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan.
Seishiro
S
Chikazawa
Yasunori
Y
Kitahara
Erika
E
Ando
Yasutomo
Y
Hori
Fumio
F
Hoshi
Kazutaka
K
Kanai
Naoyuki
N
Ito
Seiichi
S
Higuchi
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D045744:Cell Line, Tumor; D057899:Cytophagocytosis / Q000502:physiology*; D004285:Dogs; D004912:Erythrocytes / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D054747:Histiocytic Sarcoma / Q000188:drug therapy* / Q000378:metabolism
D000962:Antimalarials; D000970:Antineoplastic Agents; D037621:Artemisinins; D006418:Heme; D000077332:Artesunate; C039060:artenimol