Resveratrol Reduces the Invasive Growth and Promotes the Acquisition of a Long-Lasting Differentiated Phenotype in Human Glioblastoma Cells
Resveratrol Reduces the Invasive Growth and Promotes the Acquisition of a Long-Lasting Differentiated Phenotype in Human Glioblastoma Cells
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DOI：
10.1021/jf104917q
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发表时间：
2011-04-27
影响因子：
6.1
通讯作者：
Isidoro, Ciro
中科院分区：
文献类型：
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作者：
Castino, Roberta;Pucer, Anja;Isidoro, Ciro
恶性胶质母细胞瘤是脑肿瘤化疗中的一个挑战，因为其侵袭性行为的特点是化疗耐药性，浸润扩散，复发率和死亡率高。在这项研究中，我们使用培养的人U87 MG细胞和原代人胶质母细胞瘤培养物来测试白藜芦醇（RV）的抗癌特性，白藜芦醇是一种植物抗毒素，大量存在于各种膳食产品中。在U87 MG细胞中，100 μ M RV引起细胞生长停滞48小时和bax介导的细胞毒性96小时，并大大限制了细胞迁移和侵袭通过基质胶。在U87 MG细胞和原代胶质母细胞瘤培养物中，RV的长期给药（100 μ M，长达96小时）降低了巢蛋白（脑（癌症）干细胞标记物）的表达，但增加了胶质酸性神经元蛋白（成熟胶质细胞标记物）和β III-微管蛋白（神经元分化标记物）的表达。RV长期治疗增加了衰老相关β-半乳糖苷酶活性阳性细胞的比例。这是第一个报告显示RV诱导胶质母细胞瘤细胞的胶质样和神经元样分化的能力。慢性RV补充的有益效果持续长达96小时后，从培养基中撤出。目前的研究结果支持在星形细胞瘤的化疗方案中引入这种食物来源的分子的脉冲给药。
Malignant glioblastoma represents a challenge in the chemotherapy of brain tumors, because of its aggressive behavior characterized by chemoresistance, infiltrative diffusion, and high rate of recurrence and death. In this study, we used cultured human U87MG cells and primary human glioblastoma cultures to test the anticancer properties of resveratrol (RV), a phytoalexin abundantly present in a variety of dietary products. In U87MG cells, 100 mu M RV elicited cell growth arrest by 48 h and bax-mediated cell toxicity by 96 h and greatly limited cell migration and invasion through matrigel. Both in U87MG cells and in primary glioblastoma cultures, the chronic administration of RV (100 mu M for up to 96 h) decreased the expression of nestin (a brain (cancer) stem cells marker) but increased that of glial acidic fibrillary protein (a mature glial cell marker) and of beta III-tubulin (a neuronal differentiation marker). Chronic treatment with RV increased the proportion of cells positive for senescence-associated beta-galactosidase activity. This is the first report showing the ability of RV to induce glial-like and neuronal-like differentiation in glioblastoma cells. The beneficial effects of chronic RV supplementation lasted up to 96 h after its withdrawal from the culture medium. The present findings support the introduction of pulsed administration of this food-derived molecule in the chemotherapy regimen of astrocytomas.