University of Vermont, Burlington, Vermont, USA.
J Surg Res. 2010 Jun 15;161(2):195-201. doi: 10.1016/j.jss.2009.07.027. Epub 2009 Aug 18.
Epidemiologic studies suggest that diets high in fruits and vegetables reduce cancer risk. Resveratrol, a compound present in grapes, has been shown to inhibit a variety of primary tumors. Pterostilbene, an analogue of resveratrol found in blueberries, has both antioxidant and antiproliferative properties. We hypothesized that pterostilbene would induce apoptosis and inhibit breast cancer cell growth in vitro.
Breast cancer cells were treated with graduated doses of pterostilbene. Cell viability was measured by MTT assay. Apoptosis was evaluated via DNA fragmentation assay and TUNEL assay. Apo-ONE caspase-3/7 assay was used to evaluate caspase activity. Flow cytometry was used to evaluate mitochondrial depolarization, superoxide formation, and cell cycle. Student's t-test and two-way ANOVA with Bonferroni posttests were utilized for statistical analysis.
Pterostilbene decreased breast cancer cell viability in a concentration- and time-dependent manner. Pterostilbene treatment increased caspase-3/7 activity and apoptosis in both cell lines. Caspase-3/7 inhibitors completely reversed pterostilbene's effects on cell viability. Pterostilbene treatment triggered mitochondrial depolarization, increased superoxide anion, and caused alteration in cell cycle.
Pterostilbene treatment inhibits the growth of breast cancer in vitro through caspase-dependent apoptosis. Mitochondrial membrane depolarization and increased superoxide anion may contribute to the activation downstream effector caspases. Caspase inhibition leads to complete reversal of pterostilbene's effect on cell viability. Further in vitro mechanistic studies and in vivo experiments are warranted to determine its potential for the treatment of breast cancer.
流行病学研究表明，高水果和蔬菜饮食可降低癌症风险。白藜芦醇是葡萄中的一种化合物，已被证明能抑制多种原发性肿瘤。紫檀芪是蓝莓中白藜芦醇的类似物，具有抗氧化和抗增殖特性。我们假设紫檀芪会诱导体外乳腺癌细胞凋亡并抑制其生长。
用不同浓度的紫檀芪处理乳腺癌细胞。通过 MTT 测定法测量细胞活力。通过 DNA 片段化测定法和 TUNEL 测定法评估细胞凋亡。使用 Apo-ONE caspase-3/7 测定法评估半胱天冬酶活性。流式细胞术用于评估线粒体去极化、超氧化物形成和细胞周期。采用 Student's t 检验和双因素方差分析与 Bonferroni 事后检验进行统计学分析。
紫檀芪以浓度和时间依赖的方式降低乳腺癌细胞活力。紫檀芪处理增加了两种细胞系中的 caspase-3/7 活性和细胞凋亡。半胱天冬酶抑制剂完全逆转了紫檀芪对细胞活力的影响。紫檀芪处理引发线粒体去极化、增加超氧阴离子，并导致细胞周期改变。
紫檀芪通过 caspase 依赖性细胞凋亡抑制体外乳腺癌的生长。线粒体膜去极化和超氧阴离子的增加可能有助于下游效应半胱天冬酶的激活。半胱天冬酶抑制剂导致紫檀芪对细胞活力的作用完全逆转。需要进一步进行体外机制研究和体内实验，以确定其治疗乳腺癌的潜力。
