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首页> 外文期刊>Life sciences >Biotransformation and cytotoxic properties of NO-donors on MCF7 and U251 cell lines.
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Biotransformation and cytotoxic properties of NO-donors on MCF7 and U251 cell lines.

机译：NO供体在MCF7和U251细胞系上的生物转化和细胞毒性特性。

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摘要

Previous studies have shown a role for nitric oxide (NO) as a cytotoxic effector. In the present work, two chemically different NO-donors such as glyceryl trinitrate (GTN) and S-nitroso-N-acetylpenicillamine (SNAP) were evaluated for both NO release and cytostatic/cytotoxic properties. Nitrite accumulation in the supernatant of MCF-7 and U251 cell lines indicated a greater and quickly release of NO derived from SNAP. A time-course of hemoglobin absorption spectral changes showed a greater release of NO derived from GTN in presence of cells compared to the values observed in the media, confirming that the release of NO by GTN can be enzymatic and non-enzymatic. On the contrary, SNAP generated NO without contribution of cellular components and saturated oxyhemoglobin quickly, within 2 hours. Both NO-donors inhibited thymidine incorporation in a similar manner and dose-dependently in U251 cells, but not in MCF-7 cells, where SNAP at the highest tested dose of 1000 microM induced only a 33% cytostatic effect. About trypan blue exclusion test, after 24 h GTN and SNAP, releasing similar amounts of NO, showed comparable cytotoxic effects on U251 cells (50% dead cells), but not on MCF-7 cells, where GTN resulted more cytotoxic. From our data, the "in vitro" antitumoral activity of NO-donors seems to be related to the type of tumor cell lines, to the amount and duration of NO release.
机译：先前的研究表明一氧化氮（NO）作为细胞毒效应物的作用。在目前的工作中，评估了化学上不同的NO供体，例如三硝酸甘油酯（GTN）和S-亚硝基-N-乙酰青霉胺（SNAP）的NO释放和细胞抑制/细胞毒性特性。 MCF-7和U251细胞系上清液中的亚硝酸盐积累表明，SNAP产生的NO大量释放。与在培养基中观察到的值相比，血红蛋白吸收光谱变化的时程显示，存在细胞时，来自GTN的NO释放量更大，这证实了GTN释放的NO可以是酶促的和非酶促的。相反，SNAP在2小时内迅速生成NO，而没有细胞成分和饱和氧合血红蛋白的贡献。两种NO供体在U251细胞中均以相似的方式和剂量依赖性地抑制胸腺嘧啶核苷的掺入，而在MCF-7细胞中则无此作用，其中以最高测试剂量1000 microM的SNAP仅诱导33％的细胞抑制作用。关于台盼蓝排除试验，在GTN和SNAP释放24小时后，GTN和SNAP对U251细胞（50％死亡细胞）显示出可比的细胞毒性作用，但对GTN产生更大细胞毒性的MCF-7细胞却没有。从我们的数据来看，NO供体的“体外”抗肿瘤活性似乎与肿瘤细胞系的类型，NO释放的数量和持续时间有关。

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