Analogues of tetramethylrosamine as transport molecules for and inhibitors of P-glycoprotein-mediated multidrug resistance
Analogues of tetramethylrosamine as transport molecules for and inhibitors of P-glycoprotein-mediated multidrug resistance
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DOI：
10.1016/j.bmc.2004.06.034
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发表时间：
2004-09-01
影响因子：
3.5
通讯作者：
Detty, MR
中科院分区：
文献类型：
--
作者：
Gibson, SL;Hilf, R;Detty, MR
检测了四甲基罗斯胺及其硫代和硒代类似物（分别为TMR-O、TMR-S和TMR-Se）通过Pgp转运到耐药CR1R12细胞中的能力。与之前未暴露于维拉帕米的培养物相比，维拉帕米（7 × 10(-6) M）增强了TMR-O和TMR-S对CR1R12细胞的摄取。在7 × 10(-6) M维拉帕米存在的情况下，CR1R12细胞对TMR-O和TMR-S的摄取与不存在维拉帕米的化学敏感亲本细胞系AUXB1对TMR-O和TMR-S的摄取相当。没有一种TMR类似物单独作为CR1R12细胞的光敏剂有效。然而，在7 × 10(-6) M维拉帕米暴露2小时后，将TMR-S或TMR-Se添加到CR1R12细胞中，用5.0 J cm（-2）的350-750 nm光照射培养物产生明显的光毒性。在维拉帕米的存在下，TMR-O没有表现出明显的光毒性。化学敏感的AUXB1细胞同样容易受到使用TMR-Se的光毒性，无论之前是否暴露于维拉帕米。Pgp调节剂维拉帕米和CsA增加了CAM进入CR1R12的摄取。CR1R12细胞在黑暗中暴露于TMR-S或TMR-Se 2小时后，细胞内CAM的积累没有显著变化。然而，用TMR-S或TMR-Se孵育细胞后1小时的光暴露导致CAM摄取增加高达2倍。(C) 2004 Elsevier Ltd.版权所有。
Tetramethylrosamine and its thio- and seleno- analogues (TMR-O, TMR-S, and TMR-Se, respectively) were examined for their ability to be transported by Pgp into chemo-resistant CR1R12 cells. Verapamil (7 x 10(-6) M) enhanced the uptake of TMR-O and TMR-S into CR1R12 cells compared to those cultures not previously exposed to verapamil. The uptake of TMR-O and TMR-S in CR1R12 cells in the presence of 7 x 10(-6) M verapamil was equivalent to its uptake in the chemo-sensitive parent cell line AUXB1 in the absence or presence of verapamil. None of the TMR analogues were effective alone as photosensitizers of CR1R12 cells. However, when either TMR-S or TMR-Se was added to CR1R12 cells after 7 x 10(-6) M verapamil exposure for 2 h, irradiation of cultures with 5.0 J cm(-2) of 350-750 nm light caused significant phototoxicity. TMR-O showed no significant phototoxicity in the presence of verapamil. Chemo-sensitive AUXB1 cells are equally susceptible to phototoxicity using TMR-Se with or without previous exposure to verapamil. The Pgp modulators verapamil and CsA increased the uptake of CAM into CR1R12. Exposure of CR1R12 cells to TMR-S or TMR-Se for 2 h in the dark resulted in no significant change in the intracellular accumulation of CAM. However, 1 h of light exposure after incubation of cells with TMR-S or TMR-Se resulted in an up to 2-fold increase in CAM uptake. (C) 2004 Elsevier Ltd. All rights reserved.