PHI Remodel Chromation To Induce Growth Arrest In Liver Carcinoma SMMC-7721 Cells In Vitro

Objects To investigate PHI (phenyhexyle isothiocyanate) effect on cell apoptosis, epigenetics and the ability of mastases in hepatocellular carcinoma cell line (SMMC-7721) in vitro. We further study its potential mechanism.Methods The viability and the ability of adhesion of SMMC-7721 cells to basal membrane were observed by MTT method. Apoptotic cells were observed by TUNNEL assay. The proteins of bcl-2, aspase-9, caspase-8, caspase-3, histone acetylated H3 and H4, methylated H3K9 and H3K4 and MMP-2 and MMP-9 were detected by Western Blot.Results PHI induced a dose-dependent decrease of cells density and viability. Increasing of apoptotic cell was observed after treated with PHI. With the augmenting of time and dose, the expression of bcl-2, caspase-9, caspase-3 were decreased. In contrast, alteration of caspase-8 was not significant. It significantly induced the accumulation of acetylated histone H3, H4, and methylated H3k4 and decreased methylated H3K9. MMP-2 and MMP-9 of SMMC-7721 cells were inhibited by PHI.Conclusions PHI was able to inhibit the cell growth and induce apoptosis in SMMC-7721 cells through mitochondria pathway. Acetylation of histone H3,H4 was enhanced significantly, coupled to selective methylation of histone H3 lysine 4,followed with demethylation on lysine 9 of H3, which are marks of chromation unfolding and gene transcription. PHI could inhibit the ability of adhesion by inhibiting MMP-2 and MMP-9. It may result in anti-metastasis. PHI might be a potential novel anti-hepatocellular carcinoma agent.