新型抗增殖联苯烟酰胺：与顺铂和长春碱比较其对 MCF-7 细胞影响的 NMR 代谢组学研究。
Novel Antiproliferative Biphenyl Nicotinamide: NMR Metabolomic Study of its Effect on the MCF-7 Cell in Comparison with Cisplatin and Vinblastine.
机构信息
Department of Biological and Environmental Sciences and Technologies, University of Salento, Prov.le Lecce-Monteroni, I-73100 Lecce, Italy.
Department of Pharmacy-Pharmaceutical Sciences, University of Bari, Via Orabona 4, 70125 Bari, Italy.
出版信息
Molecules. 2020 Jul 31;25(15):3502. doi: 10.3390/molecules25153502.
A H-NMR-based metabolomic study was performed on MCF-7 cell lines treated with a novel nicotinamide derivative (DT-8) in comparison with two drugs characterized by a well-established mechanism of action, namely the DNA-metalating drug cisplatin (cis-diamminedichloridoplatinum(II), CDDP) and the antimitotic drug vinblastine (vinblastine, VIN). The effects of the three compounds, each one at the concentration corresponding to the IC value, were investigated, with respect to the controls (K), by the H-NMR of cells lysates and multivariate analysis (MVA) of the spectroscopic data. Relevant differences were found in the metabolic profiles of the different treatments with respect to the controls. A large overlap of the metabolic profiles in DT-8 vs. K and VIN vs. K suggests a similar biological response and mechanism of action, significantly diverse with respect to CDDP. On the other hand, DT8 seems to act by disorganizing the mitotic spindle and ultimately blocking the cell division, through a mechanism implying methionine depletion and/or adenosylmethionine (SAM) limitation.
一项基于 H-NMR 的代谢组学研究比较了 MCF-7 细胞系在新型烟酰胺衍生物（DT-8）处理下与两种作用机制明确的药物（顺铂（顺式二氨二氯铂(II)，CDDP）和长春碱（长春碱，VIN））的代谢产物。用细胞裂解物的 H-NMR 和光谱数据的多变量分析（MVA），研究了三种化合物（每种化合物的浓度对应于 IC 值）在对照（K）下的作用。与对照相比，不同处理的代谢谱存在明显差异。DT-8 与 K 以及 VIN 与 K 的代谢谱有很大的重叠，这表明它们具有相似的生物学反应和作用机制，与 CDDP 有显著的不同。另一方面，DT8 似乎通过扰乱有丝分裂纺锤体并最终阻止细胞分裂来发挥作用，其机制涉及蛋氨酸耗竭和/或腺苷甲硫氨酸（SAM）限制。
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