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含二茂铁基樟脑磺酰胺 DK-164 对乳腺癌细胞系的影响。

The Effect of a Ferrocene Containing Camphor Sulfonamide DK-164 on Breast Cancer Cell Lines.

机构信息

Institute of Molecular Biology, "Roumen Tsanev'', Bulgarian Academy of Sciences, bl. 21, Acad. G. Bonchev Str., Sofia 1113, Bulgaria.

Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, bl. 9, Acad. G. Bonchev Str., Sofia 1113, Bulgaria.

出版信息

Anticancer Agents Med Chem. 2019;19(15):1874-1886. doi: 10.2174/1871520619666190724094334.

Abstract

BACKGROUND

Drug resistance is a major cause of cancer treatment failure. Most cancer therapies involve multiple agents, to overcome it. Compounds that exhibit strong anti-tumor effect without damaging normal cells are more and more in the focus of research. Chemotherapeutic drugs, combining different moieties and functional groups in one molecule, can modulate different regulatory pathways in the cell and thus reach the higher efficacy than the agents, which affect only one cellular process.

METHODS

We tested the effect of recently synthesized ferrocene-containing camphor sulfonamide DK-164 on two breast cancer and one breast non-cancer cell lines. The cytotoxic effects were evaluated using the standard MTT-dye reduction and clonogenic assays. The apoptotic or autophagic effects were evaluated by Annexin v binding or LC3 puncta formation assays, respectively. Cell cycle arrest was determined using flow cytometry. Western blot and immunofluorescent analyses were used to estimate the localization and cellular distribution of key regulatory factors NFκB and p53.

RESULTS

Compound DK-164 has well pronounced cytotoxicity greater to cancer cells (MDA-MB-231 and MCF-7) compared to non-cancerous (MCF-10A). The IC50 value of the substance caused a cell cycle arrest in G1 phase and induced apoptosis up to 24 hours in both tumor cells, although being more pronounced in MCF-7, a functional p53 cell line. Treatment with IC50 concentration of the compound provoked autophagy in both tumor lines but is better pronounced in the more aggressive cancer line (MDA-MB-231).

CONCLUSION

The tested compound DK-164 showed promising properties as a potential therapeutic agent.

摘要

背景

耐药性是癌症治疗失败的主要原因。大多数癌症疗法涉及多种药物,以克服它。具有强大抗肿瘤作用而不损伤正常细胞的化合物越来越受到研究的关注。将不同的部分和官能团结合在一个分子中的化疗药物可以调节细胞中的不同调节途径,从而达到比仅影响一个细胞过程的药物更高的疗效。

方法

我们测试了最近合成的含二茂铁的樟脑磺酰胺 DK-164 对两种乳腺癌和一种乳腺癌非癌细胞系的作用。使用标准 MTT 染料还原和集落形成测定法评估细胞毒性作用。通过 Annexin v 结合或 LC3 斑点形成测定法分别评估凋亡或自噬作用。使用流式细胞术确定细胞周期停滞。使用 Western blot 和免疫荧光分析来估计关键调节因子 NFκB 和 p53 的定位和细胞分布。

结果

化合物 DK-164 对癌细胞(MDA-MB-231 和 MCF-7)的细胞毒性作用明显强于非癌细胞(MCF-10A)。该物质的 IC50 值导致细胞周期停滞在 G1 期,并在两种肿瘤细胞中诱导凋亡,尽管在功能 p53 细胞系 MCF-7 中更为明显。用化合物的 IC50 浓度处理会在两种肿瘤系中引发自噬,但在更具侵袭性的癌症系(MDA-MB-231)中更为明显。

结论

测试的化合物 DK-164 作为一种有前途的治疗剂具有良好的特性。

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