Mechanisms of prodigiosin cytotoxicity in human neuroblastoma cell lines
Mechanisms of prodigiosin cytotoxicity in human neuroblastoma cell lines
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DOI：
10.1016/j.ejphar.2007.06.054
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发表时间：
2007-10-31
影响因子：
5
通讯作者：
Ambrosio, Santiago
中科院分区：
文献类型：
--
作者：
Francisco, Roser;Perez-Tomas, Ricardo;Ambrosio, Santiago
灵芝红素是一种细菌红色素，具有细胞毒性和潜在的抗肿瘤活性，已被测试对不同的癌细胞。本研究报告了灵芝菌素对人神经母细胞瘤细胞系SH-SY5Y、IMR-32(N型)和SK-N-AS(S型)的作用及其作用机制。我们比较了灵芝菌素和不同浓度顺铂在作用24小时内的抗癌作用。灵芝菌素的作用更强，在N型神经母细胞瘤细胞中的IC50值小于1.5mM，在S型神经母细胞瘤细胞系中的IC50值在7mU M左右。我们将灵芝菌素描述为一种破坏细胞内pH梯度的质子隔离剂，并认为其主要的细胞毒性作用可能与其对线粒体的作用有关，其中它对质子到线粒体ATP合成酶的电子链运输起解偶联作用。这一作用的结果是，ATP的产量减少了，但氧气消耗没有减少。这种作用机制不同于传统化疗药物的作用机制，提示灵芝菌素可能在神经母细胞瘤的治疗中起到增强抗肿瘤药物作用的作用。(C)2007 Elsevier B.V.保留所有权利。
Prodigiosin is a bacterial red pigment with cytotoxic properties and potential antitumor activity that has been tested against different cancerous cells. In this study we report the effect and mechanisms of action of prodigiosin against different human neuroblastoma cell lines: SH-SY5Y LAN-1, IMR-32 (N-type) and SK-N-AS (S-type). We compare the anticancerous effect of prodigiosin with that of cisplatin at different concentrations during 24 h of exposure. Prodigiosin is more potent, with IC50 values lower than 1.5 mu M in N-type neuroblastoma cells and around 7 mu M in the S-type neuroblastoma cell line. We describe prodigiosin as a proton sequestering agent that destroys the intracellular pH gradient, and propose that its main cytotoxic effect could be related to its action on mitochondria, where it exerts an uncoupling effect on the electronic chain transport of protons to mitochondrial ATP synthase. As a result of this action, ATP production is reduced but without decreasing in oxygen consumption. This mechanism of action differs from those induced by conventional chemotherapeutic drugs, suggesting a possible role for prodigiosin to enhance the effect of antitumor agents in the treatment of neuroblastoma. (c) 2007 Elsevier B.V. All rights reserved.