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脱氧胆酸钠对乳腺癌细胞系的凋亡、细胞毒性和抗迁移作用及其对作为预测风险标志物的对氧磷酶1的调节作用。

The Apoptotic, Cytotoxic, and Anti-migration Effects of Sodium Deoxycholate in a Breast Cancer Cell Line and its Modulation on PON1 as a Predictive Risk Marker.

作者信息

Tülüce Yasin, Alhammud Huda, Keleş Ahmet Yasin, Köstekci Sedat

机构信息

Van Yüzüncü Yıl University, Faculty of Medicine, Department of Medical Biology, 65080 Van, Türkiye.

Van Yüzüncü Yıl University, Institute of Health Sciences, Department of Medical Biology, 65080 Van, Türkiye.

出版信息

Curr Mol Med. 2024 Oct 14. doi: 10.2174/0115665240312216241003060934.

DOI:10.2174/0115665240312216241003060934
PMID:39411938
Abstract

INTRODUCTION

Breast cancer is the most prevalent cancer among women and is usually treated with antineoplastic drugs. The present study examines the influence of sodium deoxycholate on the molecular pathways underlying apoptosis, cytotoxicity, and the modulation of PON1 in the MCF-7 breast cancer cell line. Various doses were administered to test the hypothesis that it could potentially affect cancer cells.

METHOD

The study examined the cytotoxic effect of sodium deoxycholate on MCF-7 cells and human mammary epithelial cells (CRL-4010) using the MTT method to detect its anticancer properties. Subsequently, the efficacy of the active dose on DNA fragmentation and apoptosis was examined using the apoptotic DNA ladder and Western blot methods. Additionally, oxidative stress index and cell migration tests were conducted. Notably, sodium deoxycholate did not cause DNA damage despite demonstrating cytotoxic effects on cells.

RESULTS

The study found that sodium deoxycholate increased the levels of several pro-apoptotic proteins, leading to apoptosis. Moreover, it markedly diminishes the activity of paraoxonase and arylesterase of PON1, which are predictive risk markers for cancer. Furthermore, it was found to delay cell migration in a time-dependent manner.

CONCLUSION

These findings suggest that sodium deoxycholate exhibits an antimetastatic effect in breast cancer cells, could be a valuable subject for further cancer research.

摘要

引言

乳腺癌是女性中最常见的癌症,通常采用抗肿瘤药物进行治疗。本研究考察了脱氧胆酸钠对MCF-7乳腺癌细胞系中凋亡、细胞毒性及对PON1调节的分子途径的影响。给予不同剂量以检验其可能影响癌细胞的假设。

方法

本研究采用MTT法检测脱氧胆酸钠对MCF-7细胞和人乳腺上皮细胞(CRL-4010)的细胞毒性作用,以检测其抗癌特性。随后,采用凋亡DNA梯状条带法和蛋白质免疫印迹法检测活性剂量对DNA片段化和凋亡的效果。此外,还进行了氧化应激指数和细胞迁移试验。值得注意的是,脱氧胆酸钠尽管对细胞表现出细胞毒性作用,但并未引起DNA损伤。

结果

研究发现脱氧胆酸钠增加了几种促凋亡蛋白的水平,导致细胞凋亡。此外,它显著降低了PON1的对氧磷酶和芳基酯酶的活性,而这两种酶是癌症的预测风险标志物。此外,还发现它以时间依赖性方式延迟细胞迁移。

结论

这些发现表明脱氧胆酸钠在乳腺癌细胞中表现出抗转移作用,可能是进一步癌症研究的有价值的对象。

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