Zamin Lauren L, Filippi-Chiela Eduardo C, Dillenburg-Pilla Patricia, Horn Fabiana, Salbego Christianne, Lenz Guido
Biophysics Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Cancer Sci. 2009 Sep;100(9):1655-62. doi: 10.1111/j.1349-7006.2009.01215.x. Epub 2009 May 12.
Glioma is the most frequent and malignant primary human brain tumor with dismal prognosis despite multimodal therapy. Resveratrol and quercetin, two structurally related and naturally occurring polyphenols, are proposed to have anticancer effects. We report here that resveratrol and quercetin decreased the cell number in four glioma cell lines but not in rat astrocytes. Low doses of resveratrol (10 microM) or quercetin (25 microM) separately had no effect on apoptosis induction, but had a strong effect on caspase 3/7 activation when administered together. Western blot analyses showed that resveratrol (10 microM) and quercetin (25 microM) caused a reduction in phosphorylation of Akt, but this reduction was not sufficient by itself to mediate the effects of these polyphenols. Most important, resveratrol and quercetin chronically administered presented a strong synergism in inducing senescence-like growth arrest. These results suggest that the combination of polyphenols can potentialize their antitumoral activity, thereby reducing the therapeutic concentration needed for glioma treatment.
胶质瘤是最常见且恶性程度高的原发性人脑肿瘤，尽管采用了多模式治疗，其预后仍不容乐观。白藜芦醇和槲皮素是两种结构相关的天然多酚类物质，被认为具有抗癌作用。我们在此报告，白藜芦醇和槲皮素可减少四种胶质瘤细胞系中的细胞数量，但对大鼠星形胶质细胞无此作用。低剂量的白藜芦醇（10微摩尔）或槲皮素（25微摩尔）单独使用对诱导细胞凋亡无影响，但共同给药时对半胱天冬酶3/7的激活有强烈作用。蛋白质印迹分析表明，白藜芦醇（10微摩尔）和槲皮素（25微摩尔）可导致Akt磷酸化减少，但这种减少本身不足以介导这些多酚类物质的作用。最重要的是，长期给予白藜芦醇和槲皮素在诱导衰老样生长停滞方面呈现出强烈的协同作用。这些结果表明，多酚类物质的组合可增强其抗肿瘤活性，从而降低胶质瘤治疗所需的治疗浓度。
