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Sensitivity to microcystins: A comparative study in human cell lines with and without multidrug resistance phenotype

机译:对微囊藻毒素的敏感性:在有和没有多药耐药表型的人类细胞系中的比较研究

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摘要

Multidrug resistance (MDR) is an obstacle in cancer treatment. An understanding of how tumoral cells react to oxidants can help us elucidate the cellular mechanism involved in resistance. Microcystins are cyanobacteria hepatotoxins known to generate oxidative stress. The aim of this study was to compare the sensitivity to microcystins of human tumoral cell lines with (Lucena) and without (K562) MDR phenotype. Endpoints analyzed were effective microcystins concentration to 50% of exposed cells (EC50), antioxidant enzyme activity, lipid peroxidation, DNA damage, reactive oxygen species (ROS) concentration, and tubulin content. Lucena were more resistant and showed lower DNA damage than K562 cells (P < 0.05). Although microcystins did not alter catalase activity, a higher mean value was observed in Lucena than in K562 cells. Lucena cells also showed lower ROS concentration and higher tubulin content. The higher metabolism associated with the MDR phenotype should increase ROS concentration and make for an improved antioxidant defense against the toxic effects of microcystins.
机译:多药耐药性(MDR)是癌症治疗的障碍。了解肿瘤细胞如何与氧化剂反应可以帮助我们阐明抗药性的细胞机制。微囊藻毒素是已知会产生氧化应激的蓝细菌肝毒素。这项研究的目的是比较具有(Lucena)和不具有(K562)MDR表型的人肿瘤细胞系对微囊藻毒素的敏感性。分析的终点是暴露于50%暴露细胞的有效微囊藻毒素浓度(EC50),抗氧化酶活性,脂质过氧化作用,DNA损伤,活性氧(ROS)浓度和微管蛋白含量。 Lucena比K562细胞更具抵抗力,并且显示出更低的DNA损伤(P <0.05)。尽管微囊藻毒素不会改变过氧化氢酶活性,但在Lucena中观察到的平均值比在K562细胞中更高。 Lucena细胞还显示出较低的ROS浓度和较高的微管蛋白含量。与MDR表型相关的更高的新陈代谢应增加ROS浓度,并增强抗微囊藻毒素毒性作用的抗氧化剂防御能力。

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