Schedule-Dependent Cytotoxicity of Etoposide and Cyclophosphamide in P-Glycoprotein-Expressing Human Leukemic K-562 Cells

Tazawa, Yuki; Usukubo, Ippei; Takada, Kazuki; Takekuma, Yoh; Shibayama, Yoshihiro; Sugawara, Mitsuru

Schedule-Dependent Cytotoxicity of Etoposide and Cyclophosphamide in P-Glycoprotein-Expressing Human Leukemic K-562 Cells

Tazawa, Yuki; Usukubo, Ippei; Takada, Kazuki et al.

Biological & Pharmaceutical Bulletin, 2014, 37(8), 1323-1329

Permalink : https://hdl.handle.net/2115/57262

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アクセス権	open access
URI	https://hdl.handle.net/2115/57262
タイトル	Schedule-Dependent Cytotoxicity of Etoposide and Cyclophosphamide in P-Glycoprotein-Expressing Human Leukemic K-562 Cells
著者	Tazawa, Yuki ; Usukubo, Ippei ; Takada, Kazuki ; Takekuma, Yoh ; Shibayama, Yoshihiro ; Sugawara, Mitsuru
著者名 Tazawa, Yuki
著者名 Usukubo, Ippei
著者名 Takada, Kazuki
e-Rad_Researcher 00396293 著者名 Takekuma, Yoh
著者名 Shibayama, Yoshihiro
e-Rad_Researcher 60332467 著者名 Sugawara, Mitsuru
言語	英語
キーワード	etoposide
	P-glycoprotein
	schedule
	cyclophosphamide
	cell cycle
発行日	2014-08
出版者	Pharmaceutical Society of Japan
収録物名	Biological & Pharmaceutical Bulletin
巻(号)	37(8)
ページ	1323-1329
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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
PISSN	0918-6158
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1248/bpb.b14-00207