槲皮素及其表观遗传修饰在抑制结肠癌细胞增殖中的抗癌作用的综合研究

IF 2.9 4区 医学 Q3 IMMUNOLOGY Archivum Immunologiae et Therapiae Experimentalis Pub Date : 2023-02-20 DOI:10.1007/s00005-023-00669-w
Meenu Bhatiya, Surajit Pathak, Ganesan Jothimani, Asim K. Duttaroy, Antara Banerjee
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引用次数: 10

摘要

结肠癌的病因涉及广泛的遗传和表观遗传改变,寻找有效的治疗策略具有挑战性。槲皮素显示出有效的抗增殖/凋亡特性。在本研究中,我们旨在阐明槲皮素对结肠癌细胞系的抗癌和抗衰老作用。通过体外CCK-8检测槲皮素对正常和结肠癌细胞株的抗增殖作用。为了检测槲皮素的抗衰老潜力,我们进行了胶原酶、弹性酶和透明质酸酶抑制活性的测定。表观遗传学和DNA损伤检测采用人nad依赖性脱乙酰酶Sirtuin-6、蛋白酶体20S、Klotho、Cytochrome-C和端粒酶ELISA试剂盒。此外,在结肠癌细胞上进行衰老相关的miRNA表达谱分析。槲皮素对结肠癌细胞增殖的抑制作用呈剂量依赖性。槲皮素通过调节衰老蛋白Sirtuin-6和Klotho的表达以及抑制端粒酶活性来限制端粒长度,从而抑制结肠癌细胞的生长,这从qPCR分析中可以看出。槲皮素还通过降低蛋白酶体20S水平来保护DNA损伤。miRNA表达谱分析结果显示,miRNA在结肠癌细胞中存在差异表达,并且高度上调的miRNA参与了细胞周期、增殖和转录的调控。我们的数据表明槲皮素通过调节抗衰老蛋白的表达抑制结肠癌细胞的增殖,为槲皮素在结肠癌治疗中的潜在应用提供了更好的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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A Comprehensive Study on the Anti-cancer Effects of Quercetin and Its Epigenetic Modifications in Arresting Progression of Colon Cancer Cell Proliferation

Colon cancer etiology involves a wide spectrum of genetic and epigenetic alterations, finding it challenging to find effective therapeutic strategies. Quercetin exhibits potent anti-proliferative/apoptotic properties. In the present study, we aimed to elucidate the anti-cancer and anti-aging effect of quercetin in colon cancer cell lines. The anti-proliferative effect of quercetin was assessed in vitro by CCK-8 in normal and colon cancer cell lines. To check the anti-aging potential of quercetin, collagenase, elastase, and hyaluronidase inhibitory activity assays were performed. The epigenetic and DNA damage assays were performed using the human NAD-dependent deacetylase Sirtuin-6, proteasome 20S, Klotho, Cytochrome-C, and telomerase ELISA kits. Furthermore, the aging-associated miRNA expression profiling was performed on colon cancer cells. The treatment with quercetin inhibited cell proliferation of colon cancer cells in a dose-dependent manner. Quercetin arrested colon cancer cell growth by modulating expression of aging proteins including Sirtuin-6 and Klotho and also by inhibiting telomerase activity to restrict the telomere length which is evident from qPCR analysis. Quercetin also exhibited DNA damage protection by reducing proteasome 20S levels. The miRNA expression profiling results displayed differential expression of miRNA in colon cancer cell, and in addition, the highly upregulated miRNA was involved in the regulation of cell cycle, proliferation, and transcription. Our data suggest that quercetin treatment inhibited cell proliferation in colon cancer cells through regulating the anti-aging protein expression and provides better understanding for quercetin’s potential use in colon cancer treatment.

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来源期刊
CiteScore
5.90
自引率
0.00%
发文量
26
审稿时长
>12 weeks
期刊介绍: Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is a bimonthly, multidisciplinary journal. It publishes reviews and full original papers dealing with immunology, experimental therapy, immunogenetics, transplantation, microbiology, immunochemistry and ethics in science.
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