Polyaromatic alkaloids from marine invertebrates as cytotoxic compounds and inhibitors of multidrug resistance caused by P-glycoprotein.
Polyaromatic alkaloids from marine invertebrates as cytotoxic compounds and inhibitors of multidrug resistance caused by P-glycoprotein.
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DOI：
10.1038/bjc.1996.421
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发表时间：
1996-09
影响因子：
8.8
通讯作者：
Puentes, JLF
中科院分区：
文献类型：
--
作者：
Quesada, AR;Gravalos, MDG;Puentes, JLF
本文研究了从被囊动物（Didemnum属）中分离的多芳香生物碱（lamellarins）家族几个成员对几种肿瘤细胞系生长和p -糖蛋白（P-gp）介导的多药耐药（MDR）的影响。在一组肿瘤细胞系上进行了片层蛋白的细胞毒性实验，其中包括两种多药耐药细胞系。一些片层素显示出良好的抗肿瘤活性，对抗性细胞系及其相应亲本细胞系具有相似的细胞毒性。两种片层蛋白对肺癌细胞表现出较强的抑制作用。研究人员还在耐多药耐药细胞中进行了无毒浓度下不同层状蛋白的抗性修饰活性研究，发现层状蛋白I具有最高的化学致敏活性。在无毒剂量下，维拉帕米和片藻素1在多药耐药细胞中以浓度依赖的方式有效地增加了阿霉素、vinblastine和柔红霉素的细胞毒性，但片藻素1作为MDR调节剂的效力比维拉帕米高9- 16倍。罗丹明123在多药耐药的Lo Vo/Dx细胞中的体外积累测量表明，片藻素I通过直接抑制p- gp介导的药物外排来逆转MDR。这项工作强调了利用这些海洋衍生化合物作为抗肿瘤药物的潜在新来源的可能性，这些药物对耐药细胞有活性，也可以作为耐多药表型的无毒调节剂。
The effects of several members of the family of lamellarins, polyaromatic alkaloids isolated from tunicates belonging to the genus Didemnum, on the growth of several tumour cell lines and on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR), were investigated. Cytotoxicity experiments of lamellarins were performed on a panel of tumour cell lines, including two multidrug-resistant cell lines. Some lamellarins showed good anti-tumour activity, with similar levels of cytotoxicity against both the resistant and their corresponding parental cell lines. Two lamellarins displayed a high potency against lung carcinoma cells. Studies of the resistance modifier activity of the different lamellarins at non-toxic concentrations were also carried out in cells exhibiting MDR, and lamellarin I was selected for the highest chemosensitising activity. At non-toxic doses, verapamil and lamellarin I effectively increased the cytotoxicity of doxorubicin, vinblastine and daunorubicin in a concentration-dependent manner in multidrug-resistant cells, but the potency of lamellarin I as a MDR modulator was 9- to 16-fold higher than that of verapamil. In vitro measurements of rhodamine 123 accumulation in the multidrug-resistant Lo Vo/Dx cells suggest that lamellarin I reverses MDR by directly inhibiting the P-gp-mediated drug efflux. This work underscores the possibility of using these marine-derived compounds as a potential new source of anti-tumoral drugs active on resistant cells as well as of non-toxic modulators of the MDR phenotype.
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人类结肠腺癌细胞系的分离和表征对阿霉素的抗性。
影响因子：
8.8
作者：
Grandi, M;Geroni, C;Giuliani, F C
通讯作者：
Giuliani, F C
影响因子：
8.8
作者：
Nooter K;Herweijer H
通讯作者：
Herweijer H
影响因子：
8.8
作者：
CONFORTI, G;CODEGONI, AM;BROGGINI, M
通讯作者：
BROGGINI, M
影响因子：
1.1
作者：
CARROLL, AR;BOWDEN, BF;COLL, JC
通讯作者：
COLL, JC
DOI：
10.1073/pnas.86.13.5128
发表时间：
1989-07-01
影响因子：
11.1
作者：
PEARCE, HL;SAFA, AR;BECK, WT
通讯作者：
BECK, WT