Dietary administration of Nexrutine inhibits rat liver tumorigenesis and induces apoptotic cell death in human hepatocellular carcinoma cells.
Dietary administration of Nexrutine inhibits rat liver tumorigenesis and induces apoptotic cell death in human hepatocellular carcinoma cells.
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DOI：
10.1016/j.toxrep.2014.11.006
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发表时间：
2015
影响因子：
--
通讯作者：
Ansari KM
中科院分区：
文献类型：
--
作者：
Alam S;Yadav RS;Pal A;Purshottam SK;Chaudhari BP;Das M;Ansari KM
Nexrutine 在 Solt-Farber 大鼠肝脏肿瘤发生模型中具有抗肿瘤潜力。 Nexrutine 导致 DEN/2-AAF 治疗大鼠的细胞增殖减少。它降低肝癌细胞的细胞活力并调节促凋亡和抗凋亡标记。 Nexrutine 调节细胞周期调节蛋白和 MAPK。流行病学研究表明，植物性膳食补充剂可以降低患肝癌的风险。 Nexrutine (NX) 是黄柏的一种草药提取物，已被证明具有抗炎、抗菌和抗肿瘤活性。在本研究中，我们展示了 NX 对 Solt-Farber 模型的抗肿瘤潜力，消除了 PH、二乙基亚硝胺 (DEN) 作为致癌物和 2-乙酰氨基芴 (2-AAF) 作为共致癌物诱导的大鼠肝肿瘤。在人类肝癌细胞中探索了机制途径的阐明。饮食中摄入 NX 显着降低了 DEN/2-AAF 治疗大鼠肝切片中的细胞增殖和炎症，并增加了细胞凋亡。此外，NX (2.5–10 μg/ml) 暴露显着降低了肝癌细胞的活力，并调节了 Bax 和 Bcl-2 蛋白的水平。 NX 处理导致细胞色素 c 释放增加以及半胱天冬酶 3 和 9 的裂解。此外，NX 降低了 CDK2、CDK4 以及相关细胞周期蛋白 E1 和 D1 的表达，同时上调了 p21、p27 和 p53 的表达。 NX 还增强丝裂原激活蛋白激酶 (MAPK) ERK1/2、p38 和 JNK1/2 的磷酸化。总的来说，这些发现表明，NX 介导的针对 DEN/2-AAF 诱导的肝脏肿瘤发生的保护涉及细胞增殖的减少和肝癌细胞凋亡细胞死亡的增强。
Nexrutine has anti-tumor potential in Solt-Farber rat liver tumorigenesis model. Nexrutine caused decreased cell proliferation in the DEN/2-AAF treated rats. It decreases cell viability of liver cancer cells and modulates pro- and anti-apoptotic markers. Nexrutine modulates the cell cycle regulatory proteins and MAPKs. Epidemiological studies suggested that plant-based dietary supplements can reduce the risk of liver cancer. Nexrutine (NX), an herbal extract from Phellodendronamurense, has been shown to have anti-inflammatory, anti-microbial and anti-tumor activities. In the present study, we have shown the anti-tumor potential of NX against Solt-Farber model with elimination of PH, rat liver tumor induced by diethylnitrosoamine (DEN) as carcinogen and 2-acetylaminofluorene (2-AAF) as co-carcinogen. The elucidation of mechanistic pathways was explored in human liver cancer cells. Dietary intake of NX significantly decreased the cell proliferation and inflammation, as well as increased apoptosis in the liver sections of DEN/2-AAF-treated rats. Moreover, NX (2.5–10 μg/ml) exposure significantly decreased the viability of liver cancer cells and modulated the levels of Bax and Bcl-2 proteins levels. NX treatment resulted in increased cytochrome-c release and cleavage of caspases 3 and 9. In addition, NX decreased the expression of CDK2, CDK4 and associated cyclins E1 and D1, while up-regulated the expression of p21, p27 and p53 expression. NX also enhanced phosphorylation of the mitogen-activated protein kinases (MAPKs) ERK1/2, p38 and JNK1/2. Collectively, these findings suggested that NX-mediated protection against DEN/2-AAF-induced liver tumorigenesis involves decrease in cell proliferation and enhancement in apoptotic cell death of liver cancer cells.