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黄连素可诱导多种癌细胞系发生凋亡并使细胞周期停滞。

Berberine induces apoptosis and arrests the cell cycle in multiple cancer cell lines.

作者信息

Li Qian, Zhao Hui, Chen Weimin, Huang Ping

机构信息

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Arch Med Sci. 2021 Mar 21;19(5):1530-1537. doi: 10.5114/aoms/132969. eCollection 2023.

DOI:10.5114/aoms/132969
PMID:37732040
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10507748/
Abstract

INTRODUCTION

To examine the anti-cancer effects of berberine on multiple cancer cell lines, and to clarify the underlying molecular mechanisms.

MATERIAL AND METHODS

The IC values for the action of berberine on Tca8113 (oral squamous cell carcinoma), CNE2 (nasopharyngeal carcinoma cell), MCF-7 (breast cancer), Hela (cervical carcinoma), and HT29 (colon cancer) cells were determined by MTT cell viability assay. Early apoptosis and cell cycle arrest were examined by flow cytometry with annexin V and propidium iodide (PI) staining, respectively. For expression of BAX and BCL-2 genes and proteins were detected by real-time PCR and western blotting, respectively.

RESULTS

Berberine displayed a cytotoxic effect on all the cell lines tested. The IC values were determined (Tca8113, 218.52 ±18.71; CNE2, 249.18 ±18.14; MCF-7, 272.15 ±11.06; Hela, 245.18 ±17.33; and HT29, 52.37 ±3.45). PI staining revealed that berberine treatment resulted in cell cycle arrest at G2/M. The treatment also induced early apoptosis as shown by annexin V staining. In addition, berberine significant elevated gene and protein expression of BAX, which was accompanied by substantial decreases in BCL-2 gene and protein levels. The effects of berberine on BAX and BCL-2 were time-dependent.

CONCLUSIONS

Berberine exhibited cytotoxic effects on multiple cancer cell lines by inducing apoptosis and cell cycle arrest. The BCL-2/BAX signaling pathway may be the common pathway underlying the anti-tumor effect of berberine. The findings support the notion that berberine is a dietary compound that can be further developed into a drug candidate for cancer treatment.

摘要

引言

研究黄连素对多种癌细胞系的抗癌作用,并阐明其潜在的分子机制。

材料与方法

采用MTT细胞活力测定法测定黄连素对Tca8113(口腔鳞状细胞癌)、CNE2(鼻咽癌细胞)、MCF-7(乳腺癌)、Hela(宫颈癌)和HT29(结肠癌)细胞的IC值。分别采用膜联蛋白V和碘化丙啶(PI)染色的流式细胞术检测早期凋亡和细胞周期阻滞。分别通过实时PCR和蛋白质免疫印迹法检测BAX和BCL-2基因及蛋白的表达。

结果

黄连素对所有测试的细胞系均显示出细胞毒性作用。测定了IC值(Tca8113,218.52±18.71;CNE2,249.18±18.14;MCF-7,272.15±11.06;Hela,245.18±17.33;HT29,52.37±3.45)。PI染色显示黄连素处理导致细胞周期阻滞于G2/M期。如膜联蛋白V染色所示,该处理还诱导了早期凋亡。此外,黄连素显著提高了BAX的基因和蛋白表达,同时BCL-2基因和蛋白水平大幅下降。黄连素对BAX和BCL-2的作用具有时间依赖性。

结论

黄连素通过诱导凋亡和细胞周期阻滞对多种癌细胞系表现出细胞毒性作用。BCL-2/BAX信号通路可能是黄连素抗肿瘤作用的共同途径。这些发现支持了黄连素是一种可进一步开发成为癌症治疗候选药物的膳食化合物这一观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6137/10507748/0f5a717da274/AMS-19-5-132969-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6137/10507748/988ef3d80a81/AMS-19-5-132969-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6137/10507748/6e2bdfef2147/AMS-19-5-132969-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6137/10507748/0f5a717da274/AMS-19-5-132969-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6137/10507748/988ef3d80a81/AMS-19-5-132969-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6137/10507748/6e2bdfef2147/AMS-19-5-132969-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6137/10507748/0f5a717da274/AMS-19-5-132969-g003.jpg

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