Curcumin down-regulates the multidrug-resistance mdr1b gene by inhibiting the PI3K/Akt/NFκB pathway

被引：195

作者：

Choi, Byeong Hyeok ^{[2
,4
]}

Kim, Chang Gun ^{[2
,4
]}

Lim, Yoongho ^{[3
]}

Shin, Soon Young ^{[1
]}

Lee, Young Han ^{[2
]}

机构：

[1] Hanyang Univ, Inst Nat Sci & Technol, Ansan 426791, Gyeonggi Do, South Korea

[2] Konkuk Univ, IBST, Dept Biomed Sci & Technol, Seoul 143701, South Korea

[3] Konkuk Univ, BMIC, Div Biosci & Biotechnol, Seoul 143701, South Korea

[4] Hanyang Univ, Coll Sci & Technol, Div Mol & Life Sci, Ansan 426791, Gyeonggi Do, South Korea

来源：

CANCER LETTERS | 2008年 / 259卷 / 01期

关键词：

curcumin; multidrug resistance; L1210 leukemia cell line; mdr1b gene; NF-kappa B; P-glycoprotein; phospbatidyinositol; 3-kinase; transcription; promoter activity;

D O I：

10.1016/j.canlet.2007.10.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Curcumin, a constituent of turmeric, has anti-inflammatory, anti-carcinogenic, and chemopreventive effects in several animal tumor models. The expression of P-glycoprotein (P-gp), encoded by the mdr gene, is often associated with multidrug resistance (MDR) to unrelated chemotherapeutic drugs in cancer cells. Here, we demonstrate that curcumin down-regulates P-gp expression in multidrug-resistant L1210/Adr cells. Transfection with a series of 5'-deleted constructs of the mdr1b gene promoter indicated that a proximal region between -205 and +42 of the sequence was responsible for tile suppression of promoter activity by curcumin. This response might be associated with the inhibition of the phosphatidyinositol 3-kinase (PT3K)/Akt/nuclear factor-kappa B (NF-kappa B) signaling pathway by curcumin. Moreover, curcumin reversed the MDR of the L1210/Adr cells. Thus, curcumin can contribute to the reversal of the MDR phenotype, probably due to the Suppression of P-gp expression via the inhibition of the PI3K/Akt/NF-kappa B signaling pathway. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

引用

页码：111 / 118

页数：8

共 29 条

[1] Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IκBα kinase and Akt activation [J].