Chikazawa Seishiro, Kitahara Yasunori, Ando Erika, Hori Yasutomo, Hoshi Fumio, Kanai Kazutaka, Ito Naoyuki, Higuchi Seiichi
Department of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan.
J Vet Med Sci. 2014 Mar 1;76(2):249-53. doi: 10.1292/jvms.13-0319. Epub 2013 Sep 20.
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.
抗疟药物双氢青蒿素（DHA）和青蒿琥酯（ATS）在肿瘤细胞中表现出铁依赖性细胞毒性。我们推测，红细胞吞噬摄取血红素铁可增强DHA和ATS的细胞毒性。与对照组相比，用红细胞吞噬（EP）处理犬组织细胞肉瘤细胞系DH82可显著增强DHA和ATS的细胞毒性。细胞内血红素合成抑制剂琥珀酰丙酮可降低正常细胞中DHA和ATS的细胞毒性，但在EP细胞中未观察到这种变化。这些结果表明，源自红细胞的外源性血红素可增强DHA和ATS的细胞毒性。此外，我们的研究表明，血红素可能是兽医学肿瘤治疗中的一种新成分。
