Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
Division of Radiation Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
Mar Drugs. 2019 Sep 8;17(9):525. doi: 10.3390/md17090525.
Malignant glioma (MG) is a poor prognostic brain tumor with inevitable recurrence after multimodality treatment. Searching for more effective treatment is urgently needed. Differentiation induction via epigenetic modification has been proposed as a potential anticancer strategy. Natural products are known as fruitful sources of epigenetic modifiers with wide safety margins. We thus explored the effects of oligo-fucoidan (OF) from brown seaweed on this notion in MG cells including Grade III U87MG cells and Grade IV glioblastoma multiforme (GBM)8401 cells and compared to the immortalized astrocyte SVGp12 cells. The results showed that OF markedly suppress the proliferation of MG cells and only slightly affected that of SVGp12 cells. OF inhibited the protein expressions of DNA methyltransferases 1, 3A and 3B (DNMT1, 3A and 3B) accompanied with obvious mRNA induction of differentiation markers (, , , , and ) both in U87MG and GBM8401 cells. Accordingly, the methylation of , a DNMT3B target gene, was decreased by OF. In combination with the clinical DNMT inhibitor decitabine, OF could synergize the growth inhibition and induction in U87MG cells. Appropriated clinical trials are warranted to evaluate this potential complementary approach for MG therapy after confirmation of the effects in vivo.
恶性胶质瘤（MG）是一种预后不良的脑肿瘤，经过多模态治疗后必然会复发。因此迫切需要寻找更有效的治疗方法。通过表观遗传修饰进行分化诱导已被提出作为一种潜在的抗癌策略。天然产物是具有广泛安全边际的表观遗传修饰剂的丰富来源。因此，我们研究了褐藻来源的低聚岩藻聚糖（OF）对包括 3 级 U87MG 细胞和 4 级多形性胶质母细胞瘤（GBM）8401 细胞在内的 MG 细胞的这种作用，并与永生化星形细胞瘤 SVGp12 细胞进行了比较。结果表明，OF 明显抑制 MG 细胞的增殖，而对 SVGp12 细胞的影响很小。OF 抑制 DNA 甲基转移酶 1、3A 和 3B（DNMT1、3A 和 3B）的蛋白表达，同时在 U87MG 和 GBM8401 细胞中明显诱导分化标志物（，，，，，）的 mRNA 表达。相应地，OF 降低了 DNMT3B 靶基因的甲基化。OF 与临床 DNMT 抑制剂地西他滨联合使用，可协同抑制 U87MG 细胞的生长和诱导分化。在体内实验确认其效果后，需要进行适当的临床试验来评估这种治疗 MG 的潜在互补方法。
Zotero 插件