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  • Title: [Modulation of histone acetylation and induction of apoptosis in SMMC-7721 cells by phenylhexyl isothiocyanate].
    Author: Lai YD, Ma XD, Huang YQ, Xu XN, Wang XZ, Chiao DJ, Liu D.
    Journal: Zhonghua Zhong Liu Za Zhi; 2010 Nov; 32(11):804-7. PubMed ID: 21223683.
    Abstract:
    OBJECTIVE: To investigate the effect of phenylhexyl isothiocyanate (PHI) on histone acetylation and apoptosis in hepatocellular carcinoma cell line (SMMC-7721) in vitro. METHODS: The viability of SMMC-7721 cells was determined by trypan blue exclusion. Apoptotic cells were assessed by TUNEL assay. The proteins of Bcl-2, Procaspase-9, Procaspase-8, Procaspase-3, caspase-9, caspase-3, histone acetylated H3 and H4 were detected by Western blot. RESULTS: Compared with the vehicle control, PHI at 5, 10, 20, 40 and 80 µmol/L reduced the cell viability of SMMC-7721 cells in a concentration-dependent manner. PHI induced apoptosis in SMMC-7721 cells. An increased amount of apoptotic cells was detected after 7 hours exposure to PHI at 10, 20, and 40 µmol/L, 6.9% ± 2.4%, 17.5% ± 4.2% and 54.5% ± 5.4%, respectively, while that of the vehicle control was 4.5% ± 2.3% (P < 0.05). Along with the prolongation of time and increase of dose, the expressions of bcl-2, procaspase-9, procaspase-3 were decreased, that of caspase-9 and caspase-3 was increased. In contrast, alteration of procaspase-8 was not significant at those concentrations. PHI accumulated acetylated histone H3 and H4. After 3 hours exposure to PHI at 10, 20 and 40 µmol/L, the level of histone acetylated H3 was 1.87-, 2.43-, 3.67-fold increased and histone acetylated H4 was 1.29-, 1.45-, and 2.25-fold increased, compared with that of the vehicle control. The protein of histone acetylated H3 and H4 was significantly accumulated after 7 hours exposure. CONCLUSION: PHI is a new histone deacetylation inhibitor. It may induce accumulation of histone acetylation H3 and H4, inhibit cell growth and induce apoptosis in SMMC-7721 cells via the mitochondrial pathway.
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