Inhibitory effects of (-)-epigallocatechin-3-gallate and pterostilbene on pancreatic cancer growth in vitro
Inhibitory effects of (-)-epigallocatechin-3-gallate and pterostilbene on pancreatic cancer growth in vitro
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DOI：
10.1016/j.jss.2012.04.023
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发表时间：
2012-10-01
影响因子：
2.2
通讯作者：
McFadden, David W.
中科院分区：
文献类型：
--
作者：
Kostin, Shannon F.;McDonald, Debbie E.;McFadden, David W.
背景：之前的研究表明，绿茶中天然存在的抗氧化剂(-)-表没食子儿茶素-3-没食子酸酯（EGCG）和紫菀芪（一种从蓝莓中提取的芪类化合物）在体外单独使用时可以抑制胰腺癌。我们假设EGCG和紫檀芪联合使用在体外会显示出加性效应。方法：采用胰腺癌细胞系MIA PaCa-2和PANC-1，评价其对细胞增殖和活力（3-(4,5-二甲基噻唑-2-y1)-2,5-二苯四唑溴化试验、细胞周期分析）和线粒体凋亡（线粒体去极化、细胞色素C释放、caspase-3/ 7活性、酶联免疫吸附法检测细胞死亡）的疗效和协同作用。结果：细胞增殖实验显示，紫檀芪和EGCG在72 h后对两种细胞系均有显著的加性抗增殖作用（P < 0.05）。联合用药后MIA出现s期骤停（增加10-12%）；然而，PANC未观察到细胞周期阻滞。联合用药可诱导MIA组线粒体去极化和细胞色素C上调（P < 0.05），而PANC组未见上述作用。EGCG增加MIA患者caspase-3/ 7；两种细胞的活性均未见显著提高（P < 0.05）。凋亡仅在PANC中出现（P < 0.05）。在3-(4,5-二甲基噻唑-2-y1)-2,5-二苯四唑溴联合试验中，MIA的增殖减少表明细胞死亡可能通过另一种机制发生。结论：我们的结果是令人鼓舞的，关于未来使用EGCG和紫檀芪来改善传统的胰腺癌治疗。综上所述，EGCG和紫檀芪在体外具有相加性的抗增殖作用，并通过调控两种细胞凋亡机制的不同位点改变了两种细胞的凋亡机制。(C) 2012爱思唯尔公司版权所有。
Background: It has been previously shown that the naturally occurring antioxidant (-)-epigallocatechin-3-gallate (EGCG), found in green tea, and pterostilbene, a stilbenoid derived from blueberries, inhibit pancreatic cancer in vitro when used individually. We hypothesized that the combination of EGCG and pterostilbene would reveal additive effects in vitro.Methods: Using the pancreatic cancer cell lines MIA PaCa-2 and PANC-1, efficacy and synergism were evaluated for cell proliferation and viability (3-(4,5-dimethyltiazol-2-y1)-2,5-diphenltetrazolium bromide assays, cell cycle analysis) and mitochondrial apoptosis (mitochondrial depolarization, cytochrome C release, caspase-3/ 7 activity, cell death detection using enzyme-linked immunosorbent assay).Results: Cell proliferation assays revealed significant additive antiproliferative effects with pterostilbene and EGCG in both cell lines at the later, 72-h, point (P < 0.05). MIA underwent S-phase arrest with the combination (10-12% increase); however, cell cycle arrest was not observed in PANC. The combination induced mitochondrial depolarization and upregulated cytochrome C (P < 0.05) in MIA, but these effects were not observed in PANC. EGCG increased caspase-3/ 7 in MIA; however, the combination did not significantly increase the activity in either cell line (P < 0.05). Apoptosis was only observed in PANC (P < 0.05). The reduction in proliferation in MIA in the 3-(4,5-dimethyltiazol-2-y1)-2,5-diphenltetrazolium bromide assays with the combination indicated that cell death occurs, possibly through another mechanism.Conclusions: Our results are encouraging regarding the future use of EGCG and pterostilbene to improve traditional pancreatic cancer therapies. In conclusion, EGCG and pterostilbene have additive, antiproliferative effects in vitro and alter the apoptotic mechanisms in both cell lines by modulation at different points in the mechanism. (C) 2012 Elsevier Inc. All rights reserved.