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胡萝卜戊烷类组分通过抑制MAPK和PI3K信号通路抑制人结肠腺癌HT-29细胞增殖并诱导其凋亡。

Daucus carota Pentane-Based Fractions Suppress Proliferation and Induce Apoptosis in Human Colon Adenocarcinoma HT-29 Cells by Inhibiting the MAPK and PI3K Pathways.

作者信息

Shebaby Wassim N, Bodman-Smith K B, Mansour Anthony, Mroueh Mohamad, Taleb Robin I, El-Sibai Mirvat, Daher Costantine F

机构信息

1 Department of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey , Surrey, United Kingdom .

2 School of Medicine, Lebanese American University , Byblos, Lebanon .

出版信息

J Med Food. 2015 Jul;18(7):745-52. doi: 10.1089/jmf.2014.3225. Epub 2015 Jan 19.

Abstract

Daucus carota L. ssp. carota (Apiacea, wild carrot, Queen Anne's lace) has been used in folk medicine throughout the world and recently was shown to possess anticancer and antioxidant activities. This study aims to determine the anticancer activity of the pentane fraction (F1) and the 1:1 pentane:diethyl ether fraction (F2) of the Daucus Carota oil extract (DCOE) against human colon adenocarcinoma cell lines (HT-29 and Caco-2). Treatment of cells with various concentrations of F1 or F2 fractions produced a dose-dependent inhibition of cell proliferation. Flow cytometric analysis indicated that both fractions induced sub-G1 phase accumulation and increased apoptotic cell death. Western blot revealed the activation of caspase-3, PARP cleavage, and a considerable increase in Bax and p53 levels, and a decrease in Bcl-2 level. Treatment of HT-29 cells with either fraction markedly decreased the levels of both phosphorylated Erk and Akt. Furthermore, the combined treatment of F1 or F2 with wortmannin showed no added inhibition of cell survival suggesting an effect of F1 or F2 through the phosphatidyl inositol 3-kinase (PI3K) pathway. This study proposes that DCOE fractions (F1 and F2) inhibit cell proliferation by inducing cell cycle arrest and apoptosis in HT-29 cells through the suppression of mitogen-activated protein kinase (MAPK)/Erk and PI3K/Akt pathways.

摘要

胡萝卜(伞形科,野胡萝卜,安妮女王的蕾丝花)在世界各地的民间医学中都有应用,最近被证明具有抗癌和抗氧化活性。本研究旨在确定胡萝卜油提取物(DCOE)的戊烷馏分(F1)和1:1戊烷:二乙醚馏分(F2)对人结肠腺癌细胞系(HT-29和Caco-2)的抗癌活性。用不同浓度的F1或F2馏分处理细胞会产生剂量依赖性的细胞增殖抑制作用。流式细胞术分析表明,这两种馏分均诱导亚G1期积累并增加凋亡细胞死亡。蛋白质免疫印迹显示半胱天冬酶-3的激活、聚(ADP-核糖)聚合酶的裂解,以及Bax和p53水平显著增加,Bcl-2水平降低。用任何一种馏分处理HT-29细胞均显著降低磷酸化的细胞外信号调节激酶(Erk)和蛋白激酶B(Akt)的水平。此外,F1或F2与渥曼青霉素联合处理未显示对细胞存活有额外抑制作用,提示F1或F2通过磷脂酰肌醇3-激酶(PI3K)途径发挥作用。本研究提出,DCOE馏分(F1和F2)通过抑制丝裂原活化蛋白激酶(MAPK)/Erk和PI3K/Akt途径诱导HT-29细胞周期停滞和凋亡,从而抑制细胞增殖。

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