Epigenetic modification and differentiation induction of malignant glioma cells by oligo-fucoidan

Chien Huang Liao, I. Chun Lai, Hui Ching Kuo, Shuang En Chuang, Hsin Lun Lee, Jacqueline Whang-Peng, Chih Jung Yao, Gi Ming Lai

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17 引文 斯高帕斯(Scopus)

摘要

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 (MBP, OLIG2, S100β, GFAP, NeuN and MAP2) both in U87MG and GBM8401 cells. Accordingly, the methylation of p21, a DNMT3B target gene, was decreased by OF. In combination with the clinical DNMT inhibitor decitabine, OF could synergize the growth inhibition and MBP 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.

原文英語
文章編號525
期刊Marine Drugs
17
發行號9
DOIs
出版狀態已發佈 - 9月 8 2019

ASJC Scopus subject areas

  • 藥物發現

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