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Molecular Signatures Associated with Treatment of Triple-Negative MDA-MB231 Breast Cancer Cells with Histone Deacetylase Inhibitors JAHA and SAHA
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2017-11-12 00:00:00 , DOI: 10.1021/acs.chemrestox.7b00269 Mariangela Librizzi 1 , Fabio Caradonna 1 , Ilenia Cruciata 1 , Janusz Dębski 2 , Supojjanee Sansook 3 , Michał Dadlez 2 , John Spencer 3 , Claudio Luparello 1
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2017-11-12 00:00:00 , DOI: 10.1021/acs.chemrestox.7b00269 Mariangela Librizzi 1 , Fabio Caradonna 1 , Ilenia Cruciata 1 , Janusz Dębski 2 , Supojjanee Sansook 3 , Michał Dadlez 2 , John Spencer 3 , Claudio Luparello 1
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Jay Amin hydroxamic acid (JAHA; N8-ferrocenylN1-hydroxy-octanediamide) is a ferrocene-containing analogue of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA). JAHA’s cytotoxic activity on MDA-MB231 triple negative breast cancer (TNBC) cells at 72 h has been previously demonstrated with an IC50 of 8.45 μM. JAHA’s lethal effect was found linked to perturbations of cell cycle, mitochondrial activity, signal transduction, and autophagy mechanisms. To glean novel insights on how MDA-MB231 breast cancer cells respond to the cytotoxic effect induced by JAHA, and to compare the biological effect with the related compound SAHA, we have employed a combination of differential display-PCR, proteome analysis, and COMET assay techniques and shown some differences in the molecular signature profiles induced by exposure to either HDACis. In particular, in contrast to the more numerous and diversified changes induced by SAHA, JAHA has shown a more selective impact on expression of molecular signatures involved in antioxidant activity and DNA repair. Besides expanding the biological knowledge of the effect exerted by the modifications in compound structures on cell phenotype, the molecular elements put in evidence in our study may provide promising targets for therapeutic interventions on TNBCs.
中文翻译：
与组蛋白脱乙酰基酶抑制剂JAHA和SAHA治疗三阴性MDA-MB231乳腺癌细胞相关的分子标志。
杰伊·阿明（Jay Amin）异羟肟酸（JAHA; N8-二茂铁基N 1-羟基辛二酰胺）是组蛋白脱乙酰基酶抑制剂（HDACi）亚铁酰苯胺异羟肟酸（SAHA）的含二茂铁类似物。先前已通过IC 50证明了JAHA在72 h对MDA-MB231三阴性乳腺癌（TNBC）细胞的细胞毒活性为8.45μM。发现JAHA的致死作用与细胞周期，线粒体活性，信号转导和自噬机制的扰动有关。为了收集有关MDA-MB231乳腺癌细胞如何响应JAHA诱导的细胞毒性作用的新见解，并与相关化合物SAHA进行生物学比较，我们采用了差异显示PCR，蛋白质组分析和COMET分析的组合技术，并显示出由于暴露于任一HDACis而引起的分子标记谱中的某些差异。特别是，与SAHA引起的众多变化相比，JAHA对抗氧化剂活性和DNA修复中涉及的分子标记的表达表现出了更大的选择性影响。
更新日期：2017-11-12
中文翻译：
与组蛋白脱乙酰基酶抑制剂JAHA和SAHA治疗三阴性MDA-MB231乳腺癌细胞相关的分子标志。
杰伊·阿明（Jay Amin）异羟肟酸（JAHA; N8-二茂铁基N 1-羟基辛二酰胺）是组蛋白脱乙酰基酶抑制剂（HDACi）亚铁酰苯胺异羟肟酸（SAHA）的含二茂铁类似物。先前已通过IC 50证明了JAHA在72 h对MDA-MB231三阴性乳腺癌（TNBC）细胞的细胞毒活性为8.45μM。发现JAHA的致死作用与细胞周期，线粒体活性，信号转导和自噬机制的扰动有关。为了收集有关MDA-MB231乳腺癌细胞如何响应JAHA诱导的细胞毒性作用的新见解，并与相关化合物SAHA进行生物学比较，我们采用了差异显示PCR，蛋白质组分析和COMET分析的组合技术，并显示出由于暴露于任一HDACis而引起的分子标记谱中的某些差异。特别是，与SAHA引起的众多变化相比，JAHA对抗氧化剂活性和DNA修复中涉及的分子标记的表达表现出了更大的选择性影响。
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