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An In Vitro Estimation of the Cytotoxicity and Genotoxicity of Root Extract from Leonurus sibiricus L. Overexpressing AtPAP1 against Different Cancer Cell Lines

机译:过量表达AtPAP1对不同癌细胞系Leonurus sibiricus L.的根提取物的细胞毒性和基因毒性的体外估计

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摘要

As the current cancer treatment success rate is not sufficient, interest has grown in plants as possible sources of anti-cancer compounds. One such plant with a broad spectrum of activity is Lenourus sibiricus of the family Lamiaceae. This study investigates for the first time both the genotoxic and cytotoxic activities of TR (transformed) and AtPAP1 TR (with over-expression of transcriptional factor) root extracts of Lenourus sibiricus against various cancer cell lines (CCRF-CEM, K-562 and A549). Both tested extracts showed a cytotoxic effect on CCRF-CEM and K-562 cell lines, but strongest activity was observed for the AtPAP1 TR extract. No cytotoxic effect was observed against the A549 cell line in the tested concentration range, and it was found that both tested extracts may induce apoptosis by decreasing mitochondrial membrane potential and inducing nDNA damage lesion in the TP53 region and mtDNA in ND1 (mitochondrially encoded NADH: ubiquinone oxidoreductase core subunit 1) and ND5 (mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 5) regions in K-562 and CCRF-CEM. Our results confirmed that TR and AtPAP1 TR root extracts from L. sibiricus are cytotoxic and genotoxic against different model cell lines (CCRF-CEM and K-562). However, the observed genotoxicity of both extracts needs to be confirmed by additional studies. These preclinical observations support the use of L. sibiricus with other pharmacological purposes.
机译:由于当前的癌症治疗成功率还不够,因此人们越来越关注植物作为抗癌化合物的可能来源。一种具有广泛活性的植物是唇形科的Lenourus sibiricus。这项研究首次调查了黑芒(Lenourus sibiricus)的TR(转化的)和AtPAP1 TR(具有过度表达转录因子)根提取物对多种癌细胞系(CCRF-CEM,K-562和A549)的遗传毒性和细胞毒性活性)。两种测试提取物均对CCRF-CEM和K-562细胞系具有细胞毒性作用,但对AtPAP1 TR提取物观察到最强的活性。在所测试的浓度范围内未观察到对A549细胞系的细胞毒性作用,并且发现所测试的两种提取物均可通过降低线粒体膜电位并诱导TP53区和ND1的mtDNA诱导nDNA损伤而诱导凋亡(线粒体编码的NADH:泛醌氧化还原酶核心亚基1)和ND5(线粒体编码的NADH:泛醌氧化还原酶核心亚基5)区域位于K-562和CCRF-CEM中。我们的结果证实,西伯利亚乳酸杆菌的TR和AtPAP1 TR根提取物对不同模型细胞系(CCRF-CEM和K-562)具有细胞毒性和遗传毒性。但是,观察到的两种提取物的遗传毒性都需要进一步的研究来证实。这些临床前观察结果支持西伯利亚乳酸杆菌与其他药理作用的结合使用。

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