2007年9月
Isolation and characterization of arsenite-resistant human epidermoid carcinoma KB cells
ONCOLOGY REPORTS
- 巻
- 18
- 号
- 3
- 開始ページ
- 721
- 終了ページ
- 727
- 記述言語
- 英語
- 掲載種別
- 出版者・発行元
- PROFESSOR D A SPANDIDOS
Arsenic trioxide (As2O3) has been used with success in the treatment of acute promyelocytic leukemia. However, resistance to arsenite agents reduces their efficacy. We have isolated arsenite-resistant human epidermoid carcinoma KB cells, termed KAS. KAS cells were resistant to sodium arsenite (22-fold) and showed a reduced accumulation of arsenite as a result of an active efflux mechanism. Further analysis indicated that resistance of KAS cells extended to other drugs including cisplatin (17-fold), antimony potassium tartrate (11-fold) and doxorubicin (27-fold). Although increased expression of multidrug resistance protein I (MRP1) in KAS cells was confirmed by quantitative RTPCR and immunoblot analysis, specific inhibitors of MRP1 did not completely eliminate arsenite resistance. The level of glutathione (GSH) in KAS cells was 3-fold higher than that in KB-3-1 cells, and the inhibition of GSH synthesis by buthionine sulfoximine (BSO) considerably increased the cytotoxic effect of arsenite on KAS cells. A pyridine analog, 2-[4-(diphenylmethyl)-1-piperazinyl ethyl 5(trans-4, 6-dimethyl- 1,3,2-dioxaphosphorinan-2-yl)-2, 6dimethyl-4-(3-nitrophenyl)-3-pyridine-carboxylate P oxide (PAK-104P), partially reversed the arsenite resistance and increased the arsenite accumulation in KAS cells. We suggest that the increased level of GSH is involved in arsenite resistance and an as yet unidentified arsenite transporter is expressed in the arsenite-resistant KAS cells.
- リンク情報
- ID情報
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- ISSN : 1021-335X
- Web of Science ID : WOS:000248669400030