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Open AccessArticle

Epigenetic Modification and Differentiation Induction of Malignant Glioma Cells by Oligo-Fucoidan

1
Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
2
Division of Radiation Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
3
National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan
4
Department of Radiation Oncology, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan
5
Taipei Cancer Center, Taipei Medical University, Taipei 11031, Taiwan
6
Division of Hematology and Medical Oncology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
7
Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Mar. Drugs 2019, 17(9), 525; https://doi.org/10.3390/md17090525
Received: 30 July 2019 / Revised: 31 August 2019 / Accepted: 3 September 2019 / Published: 8 September 2019
(This article belongs to the Special Issue Marine Glycobiology, Glycomics and Lectins)
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. View Full-Text
Keywords: malignant glioma; oligo-fucoidan; differentiation induction; epigenetic modification; DNA methyltransferases malignant glioma; oligo-fucoidan; differentiation induction; epigenetic modification; DNA methyltransferases
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MDPI and ACS Style

Liao, C.-H.; Lai, I.-C.; Kuo, H.-C.; Chuang, S.-E.; Lee, H.-L.; Whang-Peng, J.; Yao, C.-J.; Lai, G.-M. Epigenetic Modification and Differentiation Induction of Malignant Glioma Cells by Oligo-Fucoidan. Mar. Drugs 2019, 17, 525.

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