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槲皮素和萝卜硫素通过激活ERK/MAPK途径协同抑制乳腺癌细胞增殖

Synergistic Inhibition of Breast Carcinoma Cell Proliferation by Quercetin and Sulforaphane via Activation of the ERK/MAPK Pathway.

作者信息

Wei Ranmei, Pan Xingchen, Cai Danni, Pan Lili

机构信息

Department of Breast Diseases, Hospital of Traditional Chinese Medicine of Qiqihar, Qiqihar, Heilongjiang, China.

Department of the 0perating Room,Huaian Hospital of Huaian City, Huaian Cancer Hospital, Huaian, Jiangsu, China.

出版信息

Cell Biochem Biophys. 2025 Jun;83(2):2533-2546. doi: 10.1007/s12013-024-01662-6. Epub 2025 Jan 6.

DOI:10.1007/s12013-024-01662-6
PMID:39760839
Abstract

In the contemporary era of drug discovery, herbal treatments have demonstrated an unparalleled ability to produce anticancer drugs. An important part of the therapy of cancer is the use of plants and their by-products via analogues, which alter the tumor microenvironment and several signaling pathways. The objective of the current investigation was to conclude the rate at which the herbal medications quercetin (QT) and sulforaphane (SFN) repressed the growth of breast carcinoma cells in MDA-MB-231 by preventing the ERK/MAPK signaling systems. The cells were assessed for several studies after being subjected to different concentrations (0-70 µM) of QT and SFN (QT + SFN) for duration of 24 h. We investigated the combination that QT + SFN generated cytotoxicity using the MTT assay. The DCFH-DA staining technique was utilized to assess ROS. The protein spectra of survival of cells, cell cycle progression, and apoptosis were evaluated employing flow cytometry and western blotting. The consequences illustrated that the relative cytotoxicity of QT and SFN was roughly 28.74 μM and 39.87 μM for MDA-MB-231 cells, respectively. Following the 24-h incubation period, MDA-MB-231 cells exhibit considerable cytotoxicity when QT and SFN are combined, with IC values of 19.48 μM. Moreover, MCF-7 and MDA-MB-231 cells treated with QT and SFN concurrently showed substantial production of ROS and increased apoptotic signals. Consequently, because QT + SFN inhibit the production of ERK/MAPK/JNK/p38-based control of proliferation and cell cycle-regulating proteins, it has been considered a chemotherapeutic medication. To determine the extent to which the co-treatment induces apoptosis, more in vivo study will be required before they can be used commercially.

摘要

在当代药物研发时代,草药疗法已展现出开发抗癌药物的卓越能力。癌症治疗的一个重要部分是通过类似物使用植物及其副产品,这些物质可改变肿瘤微环境和多种信号通路。本研究的目的是确定草药槲皮素(QT)和萝卜硫素(SFN)通过抑制ERK/MAPK信号系统来抑制MDA-MB-231乳腺癌细胞生长的速率。细胞在接受不同浓度(0 - 70 μM)的QT和SFN(QT + SFN)处理24小时后,进行多项研究评估。我们使用MTT法研究QT + SFN产生细胞毒性的组合情况。采用DCFH-DA染色技术评估活性氧(ROS)。运用流式细胞术和蛋白质免疫印迹法评估细胞存活、细胞周期进程和凋亡的蛋白质谱。结果表明,QT和SFN对MDA-MB-231细胞的相对细胞毒性分别约为28.74 μM和39.87 μM。在24小时的孵育期后,当QT和SFN联合使用时,MDA-MB-231细胞表现出相当大的细胞毒性,IC值为19.48 μM。此外,同时用QT和SFN处理的MCF-7和MDA-MB-231细胞显示出大量的ROS产生和凋亡信号增加。因此,由于QT + SFN抑制基于ERK/MAPK/JNK/p38的增殖控制和细胞周期调节蛋白的产生,它被认为是一种化疗药物。为了确定联合治疗诱导凋亡的程度,在其能够商业化使用之前,还需要更多的体内研究。

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本文引用的文献

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Mechanistic study of quercetin in the treatment of hepatocellular carcinoma with diabetes via MEK/ERK pathway.槲皮素通过 MEK/ERK 通路治疗合并糖尿病的肝细胞癌的机制研究。
Int Immunopharmacol. 2024 Dec 5;142(Pt B):113194. doi: 10.1016/j.intimp.2024.113194. Epub 2024 Sep 20.
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Harnessing Sulforaphane Potential as a Chemosensitizing Agent: A Comprehensive Review.利用萝卜硫素作为化学增敏剂的潜力:综述
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Natural products targeting the MAPK-signaling pathway in cancer: overview.
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Potential mechanisms of quercetin in cancer prevention: focus on cellular and molecular targets.槲皮素在癌症预防中的潜在机制:聚焦细胞和分子靶点。
Cancer Cell Int. 2022 Aug 15;22(1):257. doi: 10.1186/s12935-022-02677-w.
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Anticancer potential of alkaloids: a key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine.生物碱的抗癌潜力:重点关注秋水仙碱、长春碱、长春新碱、长春地辛、长春瑞滨和长春胺。
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E3 ligases and deubiquitinating enzymes regulating the MAPK signaling pathway in cancers.E3 连接酶和去泛素化酶调控癌症中的 MAPK 信号通路。
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Dichotomy of the BSL phosphatase signaling spatially regulates MAPK components in stomatal fate determination.二分法的 BSL 磷酸酶信号在空间上调节了 MAPK 成分在保卫细胞命运决定中的作用。
Nat Commun. 2022 May 4;13(1):2438. doi: 10.1038/s41467-022-30254-2.
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Essential Oil: An Update of Its Phytochemistry, Biological Activities, and Safety Profile.精油:其植物化学、生物活性和安全性概况的更新。
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In Silico Screening of Natural Products as Potential Inhibitors of SARS-CoV-2 Using Molecular Docking Simulation.基于分子对接模拟的 SARS-CoV-2 潜在抑制剂的天然产物计算机筛选。
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