Cell-specific Synergic Effect of Cimicifugoside on Cytotoxicity of Methotrexate

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概要

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• Cimicifugoside is a triterpenoid originating from the rhizomes of Cimicifuga simplex, and acts to inhibit the subcellular transport of nucleosides. Cimicifugoside, when used in combination with methotrexate, showed a cell-specific synergic effect on the promonocytic leukemia cell line U937, but not on the chronic myelogenetic leukemia cell line K562. Thymidine uptake was more severely inhibited by cimicifugoside in a dose-dependent fashion in U937 than in K562. The mRNA expression of one of the equilibrative Na+-independent nucleoside transporters, ENT2, was lower in U937 than in K562. This suggests that the thymidine uptake by ENT2 of U937 is more severely affected by cimicifugoside than that of K562, resulting in a decrease in DNA synthesis by methotrexate. In addition, cimicifugoside more efficiently stimulated the activity of thymidine kinase (TK) in K562 than in U937, suggesting that K562 resisted the decrease in DNA synthesis caused by the inhibition of nucleoside transporters. Cimicifugoside bifunctionally potentiated the cell-specific cytotoxicity of methotrexate by inhibiting ENT2 and activating TK.

著者

• Ogra Yasumitsu

  Laboratory Of Chemical Toxicology And Environmental Health Showa Pharmaceutical University

• Hojo Hiroshi

  Laboratory Of Applied Microbiology School Of Food And Nutritional Sciences University Of Shizuoka

• Yawata Ayako

  Laboratory of Chemical Toxicology and Environmental Health, Showa Pharmaceutical University

• Kimura Saki

  Laboratory of Hygienic Chemistry, Showa Pharmaceutical University

• Matsushita Misato

  Laboratory of Hygienic Chemistry, Showa Pharmaceutical University

• Mochizuki Takehiro

  Laboratory of Hygienic Chemistry, Showa Pharmaceutical University

• Chikuma Toshiyuki

  Laboratory of Hygienic Chemistry, Showa Pharmaceutical University

• Ogra Yasumitsu

  Laboratory of Chemical Toxicology and Environmental Health and High Technology Research Center, Showa Pharmaceutical University

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