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一种甲氧基化槲皮素糖苷以依赖 TP53/miR-15/miR-16 的方式抑制 HCC 肿瘤进展。

A methoxylated quercetin glycoside harnesses HCC tumor progression in a TP53/miR-15/miR-16 dependent manner.

机构信息

Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.

Department of Pharmacology and Toxiciology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.

出版信息

Nat Prod Res. 2020 May;34(10):1475-1480. doi: 10.1080/14786419.2018.1509326. Epub 2018 Dec 11.

DOI:10.1080/14786419.2018.1509326
PMID:30526087
Abstract

This study focused on studying the impact of flavonoids isolated from on HCC cell lines and to further unveil their possible impact on TP53 and its downstream tumor suppressor miRNAs. Three flavonol glycosides were isolated from namely, Isorhamnetin-3-O-β-D-glucoside Quercetin-3-methoxy-3-O-(4``-acetylrhamnoside)-7-O-α-rhamnoside and Kaempferol-4-methoxy-3,7-O-dirhamnoside They showed a concentration and time dependent reduction in cellular viability and anchorage-independent growth of HCC cells. Moreover, they exhibited a decrease in the migrating capacity of HepG2 cells in a pattern similar to positive control cells. Showed the most potent effects in halting HCC tumorigenic activity (IC=36 ± 1.70 µM) and a repression of the cellular proliferation rate of HepG2 cells. Restoration of TP53 and its downstream tumor suppressor miRNAs; miR-15a, miR-16, miR-34a by was observed. Moreover, attenuation of mediated actions was shown upon using anti-miR-15a and anti-miR-16. To conclude, this study crystallizes a novel role of in harnessing HCC progression with a possible contribution of TP53/miR-15a/miR-16.

摘要

本研究集中研究从 中分离出的类黄酮对 HCC 细胞系的影响,并进一步揭示它们对 TP53 及其下游肿瘤抑制 miRNA 的可能影响。从 中分离出三种黄酮醇糖苷,即异鼠李素-3-O-β-D-葡萄糖苷、槲皮素-3-甲氧基-3-O-(4``-乙酰鼠李糖苷)-7-O-α-鼠李糖苷和山奈酚-4-甲氧基-3,7-O-二鼠李糖苷。它们表现出浓度和时间依赖性降低 HCC 细胞的细胞活力和锚定非依赖性生长。此外,它们表现出 HepG2 细胞迁移能力的降低,模式类似于阳性对照细胞。 表现出最有效的抑制 HCC 肿瘤发生活性的作用(IC=36±1.70µM),并抑制 HepG2 细胞的细胞增殖率。观察到 通过 恢复 TP53 和其下游肿瘤抑制 miRNA;miR-15a、miR-16 和 miR-34a。此外,在用抗 miR-15a 和抗 miR-16 处理后,观察到 介导的作用减弱。总之,本研究阐明了 在控制 HCC 进展中的新作用,TP53/miR-15a/miR-16 可能有贡献。

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