Abstract
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.
Highlights
Cancer is widely considered as a developmental disease, caused by the dysregulation of cellular proliferation and differentiation [1,2]
The sulfate contents in both fucoidans are similar [38], suggesting that the anticancer activity of fucoidan could be considerably improved by lowering the molecular weight
As far as we know, no literature has shown the effects of OF on Malignant glioma (MG) cells
Summary
Cancer is widely considered as a developmental disease, caused by the dysregulation of cellular proliferation and differentiation [1,2]. Cancer cells generally belong to incomplete cell differentiation mainly in profound impairment of terminal differentiation. Substantial evidence has revealed that this highly de-differentiated and plastic state reflects acquisition of genetic events that actively promote stemness [3]. Tumors originate from cells with stem cell characteristics that have acquired aberrant gene expression patterns, mostly due to mutations and epimutations. Mar. Drugs 2019, 17, 525; doi:10.3390/md17090525 www.mdpi.com/journal/marinedrugs
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