Schedule-Dependent Cytotoxicity of Etoposide and Cyclophosphamide in P-Glycoprotein-Expressing Human Leukemic K-562 Cells
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- Tazawa Yuki
- Laboratory of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Hokkaido University
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- Usukubo Ippei
- Laboratory of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Hokkaido University
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- Takada Kazuki
- Laboratory of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Hokkaido University
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- Takekuma Yoh
- Laboratory of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Hokkaido University
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- Shibayama Yoshihiro
- Education Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokkaido University
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- Sugawara Mitsuru
- Laboratory of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Hokkaido University Education Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokkaido University
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抄録
Combination chemotherapy is often used to treat cancer. Many studies have shown schedule-dependent effects between anticancer drugs. Our previous studies showed that K-562 cells pretreated with non-cytotoxic concentrations of 4-hydroperoxycyclophosphamide (4-HPC), which is a preactivated analog of cyclophosphamide (CY), enhanced the cytotoxicity of etoposide (VP-16). The appearance of cellular resistance to anticancer drugs is a major problem in cancer chemotherapy. P-Glycoprotein (P-gp) plays an important role in drug resistance, and VP-16 is a substrate for this efflux pump. In the present study, we demonstrated schedule-dependent cytotoxicity of VP-16 and CY in P-gp-overexpressed K-562/P-gp cells. Cytotoxicity of VP-16 was enhanced in K-562/P-gp cells that were pretreated with a non-cytotoxic concentration of 4-HPC compared to that of cells not treated with 4-HPC. 4-HPC arrested the cell cycle at S phase. Cells in S phase are most sensitive to VP-16. The results suggest that cell cycle arrest by 4-HPC pretreatment may be responsible for the enhanced cytotoxicity of VP-16. The findings in this study should lead to improvements in clinical combination chemotherapy.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 37 (8), 1323-1329, 2014
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679608921472
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- NII論文ID
- 130004677540
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC2cbos1KisQ%3D%3D
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- ISSN
- 13475215
- 09186158
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- HANDLE
- 2115/57262
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- NDL書誌ID
- 025609980
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- PubMed
- 25087953
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- 本文言語コード
- en
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- データソース種別
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- IRDB
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