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Benth在二维和三维模型中阻滞细胞周期、诱导细胞凋亡并抑制MCF-7和MDA-MB-231细胞系的侵袭。

Benth Arrests the Cell Cycle, Induces Apoptosis and Inhibits the Invasion of MCF-7 and MDA-MB-231 Cell Lines in 2D and 3D Models.

作者信息

Martínez-Méndez Diana Del Carmen, Sánchez-Mundo María de la Luz, Ortiz-León Laura Adriana, Álvarez-Salas Luis Marat, Rosales-García Víctor Hugo, Rodríguez-Campos Jacobo, Jaramillo-Flores María Eugenia

机构信息

Ingeniería Bioquímica, Escuela Nacional de Ciencias Biológicas (ENCB)-Instituto Politécnico Nacional, Ciudad de Mexico 07738, Mexico.

ITS de Las Choapas, Tecnológico Nacional de México, Carretera Las Choapas-Cerro de Nanchital Km 6.0, Col. J. Mario Rosado, Las Choapas 96980, Mexico.

出版信息

Int J Mol Sci. 2025 Jun 13;26(12):5672. doi: 10.3390/ijms26125672.

DOI:10.3390/ijms26125672
PMID:40565136
Abstract

Breast cancer is a disease with a high incidence and mortality rate worldwide. There is a growing interest in the search for alternative treatments with a good cytotoxic effect but fewer adverse effects, because paclitaxel and cis-platinum treatments present severe adverse effects. The aim of this study was evaluating the antitumor activity of ethyl acetate extract of Benth (EAB) in breast cancer cell lines. The IC50 of EAB is 49.3 μg/mL and 3.7 μg/mL in 2D and 375 μg/mL and 135 μg/mL in 3D in the MCF-7 and MDA-MB-231 cell lines, respectively. It arrested the cell cycle in the G1 phase and decreased CDK4 activity by 86%, increasing the p53 protein levels. During the in silico analysis, the compounds interacted with the IGF-R1, CDK1, CDK2, TNFR1, MLKL, MMP2, MMP9, E-cadherin and N-cadherin proteins, which are involved in necroptosis, invasion and the cell cycle. It decreased the ATP levels in 3D by 87% at 600 μg/mL in MCF-7 and 99% at 250 μg/mL in MDA-MB-231; induced apoptosis by increasing the activity of caspases-3/7, -8 and -9; inhibited invasion and enhanced the effect of cisplatin and paclitaxel in combination with EAB. The results show the antitumor potential of EAB as a possible adjuvant in breast cancer therapy.

摘要

乳腺癌是一种在全球范围内发病率和死亡率都很高的疾病。由于紫杉醇和顺铂治疗存在严重的副作用,人们越来越有兴趣寻找具有良好细胞毒性作用但副作用较少的替代治疗方法。本研究的目的是评估多花黄精乙酸乙酯提取物(EAB)对乳腺癌细胞系的抗肿瘤活性。在MCF-7和MDA-MB-231细胞系中,EAB在二维培养中的IC50分别为49.3μg/mL和3.7μg/mL,在三维培养中的IC50分别为375μg/mL和135μg/mL。它使细胞周期停滞在G1期,使CDK4活性降低86%,增加p53蛋白水平。在计算机分析过程中,这些化合物与IGF-R1、CDK1、CDK2、TNFR1、MLKL、MMP2、MMP9、E-钙黏蛋白和N-钙黏蛋白相互作用,这些蛋白参与坏死性凋亡、侵袭和细胞周期。在MCF-7中,600μg/mL时EAB使三维培养中的ATP水平降低87%,在MDA-MB-231中,250μg/mL时降低99%;通过增加半胱天冬酶-3/7、-8和-9的活性诱导细胞凋亡;抑制侵袭,并增强顺铂和紫杉醇与EAB联合使用的效果。结果显示EAB作为乳腺癌治疗中一种可能的辅助药物具有抗肿瘤潜力。

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本文引用的文献

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Molecules. 2025 Feb 9;30(4):800. doi: 10.3390/molecules30040800.
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Antioxidant and Photoprotective Activities of 3,4-Dihydroxybenzoic Acid and (+)-Catechin, Identified from Extract, in UVB-Irradiated HaCaT Cells.从提取物中鉴定出的3,4-二羟基苯甲酸和(+)-儿茶素在紫外线B照射的HaCaT细胞中的抗氧化和光保护活性
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Breast cancer: pathogenesis and treatments.
乳腺癌:发病机制与治疗方法
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Apoptosis: A Comprehensive Overview of Signaling Pathways, Morphological Changes, and Physiological Significance and Therapeutic Implications.细胞凋亡:信号通路、形态变化、生理意义及治疗意义的全面概述。
Cells. 2024 Nov 6;13(22):1838. doi: 10.3390/cells13221838.
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TEX19 increases the levels of CDK4 and promotes breast cancer by disrupting SKP2-mediated CDK4 ubiquitination.TEX19通过破坏SKP2介导的CDK4泛素化增加CDK4水平并促进乳腺癌。
Cancer Cell Int. 2024 Jun 12;24(1):207. doi: 10.1186/s12935-024-03384-4.
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Overcoming Chemotherapy Resistance in Metastatic Cancer: A Comprehensive Review.克服转移性癌症中的化疗耐药性:综述
Biomedicines. 2024 Jan 15;12(1):183. doi: 10.3390/biomedicines12010183.
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