Molecular characterization of the grape seeds extract's effect against chemically induced liver cancer: In vivo and in vitro analyses.

Molecular characterization of the grape seeds extract's effect against chemically induced liver cancer: In vivo and in vitro analyses.
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葡萄种子提取物对化学诱导肝癌的作用的分子表征:体内和体外分析。

DOI:
10.1038/s41598-018-19492-x
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发表时间:
2018-01-19
期刊:
影响因子:
4.6
通讯作者:
Amin A
Amin A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hamza AA;Heeba GH;Elwy HM;Murali C;El-Awady R;Amin A

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本研究的目的是利用二乙基亚硝胺 (DEN) 和 2-乙酰氨基芴 (2-AAF) 相结合的两阶段致癌模型,研究葡萄籽提取物 (GSE) 在肝癌早期阶段的抗癌特性。在促销期开始时开始给予 GSE,剂量为每天 25、50 和 100mg/kg,并持续 14 周。 GSE 显着抑制肿瘤前病灶形成,并显着降低 DEN-2AAF 治疗大鼠肝脏中胎盘谷胱甘肽-S-转移酶的数量和面积,分别减少约 4 倍和 10 倍。 GSE 的作用与诱导细胞凋亡、减少细胞增殖、减少氧化应激以及下调组蛋白脱乙酰酶活性和炎症标志物(例如肝脏中环氧合酶 2、诱导型一氧化氮合酶、核因子-κ B-p65 和 p-磷酸化肿瘤坏死因子受体)表达有关。 GSE 处理还降低了 HepG2 细胞的活力,并通过激活 caspase-3 和 Bax 诱导早期和晚期细胞凋亡。此外,GSE 诱导 G2/M 和 G1/S 细胞周期停滞。本研究提供的证据表明,GSE 的抗癌作用是通过抑制细胞增殖、诱导细胞凋亡、调节氧化损伤和抑制炎症反应来介导的。
The purpose of this study was to investigate the anti-cancer property of grape seed extract (GSE) during early stages of developing liver cancer using a two-stage carcinogenic model combining diethylnitrosamine (DEN) and 2-Acetyl Aminofluorene (2-AAF). Administration of GSE at doses 25, 50 and 100 mg/kg per day started at the beginning of promotion periods and continued for 14 weeks. GSE dramatically inhibited pre-neoplastic foci formation as well as significantly decreased the number and the area of placental glutathione-S-transferase in livers of DEN-2AAF-treated rats by approximately 4 & 10 fold deductions, respectively. GSE’s effects were associated with induced apoptosis, reduced cell proliferation, decreased oxidative stress and down regulation of histone deacetylase activity and inflammation makers, such as cyclooxygenase 2, inducible nitric oxide synthase, nuclear factor-kappa B-p65 and p- phosphorylated tumor necrosis factor receptor expressions in liver. GSE treatment also decreased the viability of HepG2 cells and induced early and late apoptosis through activating caspase-3 and Bax. Furthermore, GSE induced G2/M and G1/S cell cycle arrest. The present study provides evidence that the GSE’s anticancer effect is mediated through the inhibition of cell proliferation, induction of apoptosis, modulating oxidative damage and suppressing inflammatory response.
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