HepG2 cells undergoes postmitotic neuron-like differentiation in response to inhibition of epigenetic factors

Cancer cells are not fully differentiated cells. Re-differentiation of cancer cells is expected to drive the loss of cancer cell malignancy. We found that upon the treatment of a combination of inhibitors against class I HDACs, DNMTs, EZH2 and LSD1, the hepatocellular carcinoma cell line HepG2 shows neuron like differentiation. We used microarray to analyze global gene expression change in HepG2 cells after differentiation induced by chemical treatment. HepG2 cells were treated with a combination of HDAC inhibitor TSA, DNMT inhibitor AZA, EZH2 inhibitor EPZ-6438 and LSD1 inhibitor SP2509 in appropriate doses. Cells underwent significant morphological change after eight days of treatment, as compared with HepG2 cells treated with vehicle (DMSO). Vehicle treated cells, which served as a control, and chemical inhibitor combination treated cells were collected and subjected to microassay analysis. Two samples, one was HepG2 cells treated with DMSO and the other was HepG2 cells treated with inhibitor combination, were used for microarray assay.