Reversal of P-glycoprotein and multidrug resistance-associated protein 1 mediated multidrug resistance in cancer cells by HZ08 isomers, tetrataisohydroquinolin derivatives

doi:10.1248/bpb.31.1258

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物靶标结构与功能中心

	Reversal of P-glycoprotein and multidrug resistance-associated protein 1 mediated multidrug resistance in cancer cells by HZ08 isomers, tetrataisohydroquinolin derivatives
	Yan, Fang 1; Jiang, Yi2 ; Li, Yun-Man 1; Zhen, Xia 1; Cen, Juan 1; Fang, Wei-Rong 1
刊名	BIOLOGICAL & PHARMACEUTICAL BULLETIN
	2008-06
卷号	31 期号:6 页码:1258-1264
关键词	P-glycoprotein multidrug resistance protein 1 multidrug resistance HZ08
ISSN号	0918-6158
DOI	10.1248/bpb.31.1258
文献子类	Article
英文摘要	Overexpression of P-glycoprotein (Pgp) and multidrug resistance protein 1 (MRP1) by tumors results in multidrug resistance (MDR) to structurally unrelated anti-tumor agents. HZ08, a chiral compound, was a newly synthesized tetraisohydroquinoline derivative to reverse Pgp and MRP1 mediated MDR. In present studies, R, S-HZ08 and their racemate reversed the resistance to adriamycin and vincristine of adriamycin-selected human leukemia (K562/ADM) cells that overexpress Pgp. R, S-HZ08 and their racemate modulated adriamycin cytotoxicity when R, S-HZ08 and their racemate were removed 12 h prior to the cytotoxicity assay. In addition, R, S-HZ08 and their racemate increased intracellular accumulation of Rhodamine123 in Caco-2 cells that overexpress Pgp. Furthermore, using a DNA content analysis and an annexin V binding assay, R, S-HZ08 and their racemate effectively reversed the resistance to adriamycin-induced apoptosis in K562/ADM cells. R, S-HZ08 and their racemate also moderately reversed the resistance to adriamycin and vincristine of MCF-7/ADM cells that overexpress MRP1. However, R, S-HZ08 and their racemate hardly affected intracellular glutathione (GSH) levels and glutathione S-transferase (CST) activities in MCF-7/ADM cells. The result showed that R,S-HZ08 and their racemate possibly reverse MDR1 mediated multidrug resistance by a direct interaction with MRP1, not interaction with MRP1 via GSH. Thus, R, S-HZ08 and their racemate should be useful for treating patients with tumors that overexpress both Pgp and MRP1.
资助项目	Chinese National High Technology[2002AA233071]
WOS关键词	ABC TRANSPORTERS ; LEUKOTRIENE C-4 ; LUNG-CANCER ; GLUTATHIONE ; APOPTOSIS ; MRP1 ; EXPRESSION ; VERAPAMIL ; AGENTS ; DRUGS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	PHARMACEUTICAL SOC JAPAN
WOS记录号	WOS:000258634800038
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272901]
专题	药物靶标结构与功能中心
通讯作者	Li, Yun-Man
作者单位	1.China Pharmaceut Univ, Dept Physiol, Nanjing 210009, Peoples R China; 2.Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Yan, Fang,Jiang, Yi,Li, Yun-Man,et al. Reversal of P-glycoprotein and multidrug resistance-associated protein 1 mediated multidrug resistance in cancer cells by HZ08 isomers, tetrataisohydroquinolin derivatives[J]. BIOLOGICAL & PHARMACEUTICAL BULLETIN,2008,31(6):1258-1264.
APA	Yan, Fang,Jiang, Yi,Li, Yun-Man,Zhen, Xia,Cen, Juan,&Fang, Wei-Rong.(2008).Reversal of P-glycoprotein and multidrug resistance-associated protein 1 mediated multidrug resistance in cancer cells by HZ08 isomers, tetrataisohydroquinolin derivatives.BIOLOGICAL & PHARMACEUTICAL BULLETIN,31(6),1258-1264.
MLA	Yan, Fang,et al."Reversal of P-glycoprotein and multidrug resistance-associated protein 1 mediated multidrug resistance in cancer cells by HZ08 isomers, tetrataisohydroquinolin derivatives".BIOLOGICAL & PHARMACEUTICAL BULLETIN 31.6(2008):1258-1264.