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首页> 外文期刊>RSC Advances >Chitosan promotes ROS-mediated apoptosis and S phase cell cycle arrest in triple-negative breast cancer cells: evidence for intercalative interaction with genomic DNA
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Chitosan promotes ROS-mediated apoptosis and S phase cell cycle arrest in triple-negative breast cancer cells: evidence for intercalative interaction with genomic DNA

机译：壳聚糖促进了三阴性乳腺癌细胞中的ROS介导的细胞凋亡和S期细胞周期停滞：与基因组DNA相互作用相互作用的证据

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摘要

Chitosan (CS) is a semi-synthetic bio-based polysaccharide with promising biological and antitumor properties. However, its possible underlying anticancer mechanisms and molecular interactions have remained largely unknown. Herein, we have shown that CS exerts an inhibitory effect on the proliferation of MDA-MB-231, MCF-7 and T47D breast cancer cells in a dose and time-dependent manner while being non-toxic to fibroblast L929 normal cells. Exposure of MDA-MB-231 cells to CS led to depolarization of the mitochondrial membrane, increase in ROS, DNA oxidation, and S phase cell cycle arrest. Furthermore, EB/AO staining, Annexin-PI staining, TUNEL assay, and altered expression of caspase 3 in MDA-MB-231 cells all indicated that cancer cells progressively became apoptotic upon CS exposure. S phase arrest in MDA-MB-231 cells suggests possible CS-DNA interaction. UV-visible spectroscopy confirmed CS interaction with DNA, and competitive displacement fluorescence assay revealed a binding constant of 7.6 x 10(5) M-1 for CS. In addition, its binding modes with DNA were established by CD analysis. These results clearly indicate that along with being a safe biopolymer to normal cells, CS can be considered as an effectual anticancer agent.
机译：壳聚糖（CS）是一种半合成生物基多糖，具有有前景的生物和抗肿瘤性质。然而，其可能的抗癌机制和分子相互作用在很大程度上是未知的。在此，我们已经表明，CS以剂量和时间依赖性方式对MDA-MB-231，MCF-7和T47D乳腺癌细胞增殖的抑制作用施加对MDA-MB-231，MCF-7和T47D乳腺癌细胞的增殖，同时对成纤维细胞L929正常细胞无毒。 MDA-MB-231细胞暴露于CS导致线粒体膜的去极化，ROS增加，DNA氧化和S期细胞周期停滞。此外，在MDA-MB-231细胞中，eB / AO染色，子蛋白-PI染色，TUNEL测定和随着CASPase 3的改变表达均表明癌细胞在CS暴露时逐渐变为凋亡。 MDA-MB-231细胞中的S期捕获表明可能的CS-DNA相互作用。 UV可见光谱证实CS与DNA相互作用，竞争性位移荧光测定显示CS的粘合常数为7.6×10（5）m-1。此外，通过CD分析建立其具有DNA的结合模式。这些结果清楚地表明，作为正常细胞的安全生物聚合物，Cs可以被认为是有效的抗癌剂。

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