Effect of epigenetic modulation on cancer sphere.

Background : Cancer stem cell properties are highly relevant to the biology of treatment-resistant cancers. Epigenetic modification regulates gene expressions by chromatin remodeling during malignant transformation. The aim of this study was to elucidate the possible strategy for cancer stem cells focusing on epigenetic modification. Methods : We made cancer sphere from HepG2 cells, and we added Histone deacetylase (HDAC) inhibitor, valproic acid to cancer sphere. And we compared methylation status and the gene expression between normal HepG2 and cancer sphere groups, and between cancer sphere and sphere with HDAC inhibitor treatment groups. Results : Valproic acid (VPA) cancelled this spheroid formation. In comparison between normal HepG2 and cancer sphere, the number of methylation status changes more than 0.1 of beta level was 826 probes, and we could isolate some epithelial-mesenchymal transition (EMT) related genes. And VPA reduced the expressions of EMT related genes in sphere with RT-PCR. On the other hand, in comparison between cancer sphere and sphere with VPA treatment, we detected 29 probe of methylation status change, and VPA reduced the expressions of Bcl6 in sphere. Conclusions : HDAC inhibitor affected the methylation status of cancer stem cells. Histone-acetylation might overcome treatmet-resistant cancer through the regulation of cancer stem cell.