Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells.
Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells.
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DOI：
10.1186/1476-4598-9-47
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发表时间：
2010-03-02
期刊：
影响因子：
37.3
通讯作者：
Batchu RB
中科院分区：
文献类型：
--
作者：
Bryant CS;Kumar S;Chamala S;Shah J;Pal J;Haider M;Seward S;Qazi AM;Morris R;Semaan A;Shammas MA;Steffes C;Potti RB;Prasad M;Weaver DW;Batchu RB
萝卜硫醚(SFN)是一种异硫氰酸酯植物化学物质，主要存在于十字花科蔬菜中，如甘蓝和西兰花，被认为是一种有前途的抗癌化学防腐剂。体外暴露于SFN似乎可以诱导多种类型肿瘤的细胞凋亡和细胞周期停滞。然而，在上皮性卵巢癌细胞(EOC)中，SFN抑制细胞周期进展的分子机制却知之甚少。本研究的目的是了解SFN影响EoC细胞生长和增殖的信号机制。在5~20μM浓度范围内，SFN对MDAH2774和SKOV-3细胞的生长抑制作用呈剂量依赖性，IC50值为~8μM。与化疗药物紫杉醇联合治疗可导致相加生长抑制。8μM的SFN使MDAH2774和SKOV-3细胞在第1天的生长分别减少了40%和20%。经细胞毒浓度的SFN处理的细胞通过增加Bak/Bcl2比值和裂解原天冬氨酸蛋白酶-9和多聚ADP-核糖聚合酶(PARP)来减少细胞迁移和增加细胞凋亡性死亡。细胞周期调节蛋白基因表达谱分析显示，肿瘤抑制因子视网膜母细胞瘤蛋白(Rb)表达增加，E2F-1转录因子表达降低。SFN通过下调Rb磷酸化，保护Rb-E2F-1复合体，使细胞周期停滞于G1期。SFN诱导EOC细胞生长停滞和凋亡。抑制视网膜母细胞瘤(Rb)的磷酸化和降低游离E2F-1水平似乎在EOC生长停滞中起重要作用。
Sulforaphane (SFN), an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC). The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC. SFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose)-polymerase (PARP). Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB) and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex. SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB) phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.
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影响因子：
50.5
作者：
Ozols, R. F.
通讯作者：
Ozols, R. F.
影响因子：
11.2
作者：
Choi, S;Singh, SV
通讯作者：
Singh, SV
DOI：
10.1111/j.1525-1438.2007.01044.x
发表时间：
2008-05-01
影响因子：
4.8
作者：
Suh, D. S.;Yoov, M. S.;Kim, J. Y.
通讯作者：
Kim, J. Y.
影响因子：
8.8
作者：
Singh, R. K.;Lange, T. S.;Brard, L.
通讯作者：
Brard, L.
DOI：
10.1196/annals.1378.073
发表时间：
2006-01-01
期刊：
SIGNAL TRANSDUCTION PATHWAYS, PT B
影响因子：
--
作者：
Reimer, Daniel;Sadr, Susann;Zeimet, Alain G.
通讯作者：
Zeimet, Alain G.