Sulforaphane induces apoptosis in human hepatic cancer cells through inhibition of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase4, mediated by hypoxia inducible factor-l-dependent pathway
Sulforaphane induces apoptosis in human hepatic cancer cells through inhibition of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase4, mediated by hypoxia inducible factor-l-dependent pathway
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DOI：
10.1016/j.bbapap.2011.05.015
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发表时间：
2011-10-01
影响因子：
3.2
通讯作者：
Nam, Myeong Jin
中科院分区：
文献类型：
--
作者：
Jeon, Young Keul;Yoo, Dong Ryeol;Nam, Myeong Jin
萝卜硫素（SFN）的抗癌活性最近已在几种癌细胞系中进行了研究，包括人肝癌。然而，SFN诱导人肝癌细胞死亡的机制仍然没有很好的理解。本研究旨在通过蛋白质组学分析探讨SFN诱导肝癌细胞凋亡的可能机制。双向电泳（2-DE）为基础的蛋白质组学分析用于鉴定SFN诱导的细胞凋亡的可能的靶相关蛋白。在11个被鉴定为受调控的蛋白质中，我们专注于6-磷酸果糖-2-激酶/果糖-2，6-二磷酸酶4（PFKFB 4）蛋白的下调，该蛋白被认为是糖酵解的关键调节剂。我们还发现SFN下调了转录因子缺氧诱导因子-1 α（HIF-1 α）的表达，HIF-1 α强烈调节PFKFI 34的表达。为了获得对HIF-1a和SFN的相关性的广泛理解，我们观察了对HIF-1a活性的调节剂-促分裂原活化蛋白激酶的活性的抑制。我们的研究结果表明，SFN是一个有效的诱导凋亡的肝细胞癌细胞通过PFKFB 4抑制途径。HIF-1通路抑制可能通过抑制促分裂原活化蛋白激酶介导。(C)2011 Elsevier B. V.保留所有权利。
The anti-cancer activity of sulforaphane (SFN) has recently been investigated in several cancer cell lines, including human hepatic cancers. However, the mechanism of SFN-induced cell death in human hepatic cancer cells is still not well understood. The aim of the present work is to explore the possible mechanisms of SFN-induced apoptosis in hepatocellular carcinoma cells using proteomic analysis. A two-dimensional electrophoresis (2-DE)-based-proteomic analysis was employed for identification of possible target-related proteins of SFN-induced apoptosis. Among eleven proteins identified as regulated, we focused on the downregulation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase4 (PFKFB4) protein, which has been known as a key modulator of glycolysis. We also showed that SFN down-regulated the expression of the transcriptional factor, hypoxia inducible factor-1 alpha (HIF-1 alpha), which strongly regulates PFKFI34 expression. In order to obtain a broad understanding of the correlation of HIF-1a and SFN, we observed the inhibition of the activity of mitogen-activated protein kinases, regulators of HIF-1a activity. Our findings suggest that SFN is a potent inducer of apoptosis in hepatocellular carcinoma cells via PFKFB4-inhibition pathways. HIF-1 pathway inhibition may be mediated by the inhibition of mitogen-activated protein kinases. (C) 2011 Elsevier B.V. All rights reserved.