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PHI Remodel Chromation To Induce Growth Arrest In Molt-4 Cells In Vitro

Posted on:2007-07-07Degree:MasterType:Thesis
Country:ChinaCandidate:Y Q HuangFull Text:PDF
GTID:2144360185985061Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objects To investigate the effect of PHI on normal volunteers'mononuclear cells and acute lymphoblastic leukemia (Molt -4 cells line) in vitro,we observed the state of epigenetics in Molt-4 cells after exposure to PHI, discussed the potential mechanism.Methods The viability and apoptosis of mononuclear cells were observed by trypanblue counting and TUNNEL assay. The viability of Molt-4 cells was observed by MTT method and clone suppression test. Apoptotic rate and cell cycle arrest were measured by flow cytometry. the variation of bcl-2,caspase-9, caspase-8, caspase-3,PRAP protein, acetylated H3 and H4, methylated H3K9 and H3K4 were detected by Western Blotting.Results The results showed that PHI induced a dose-dependent decrease of cells density and viability. Increasing of apoptotic cell and cell cycle blocking in G0/G1 were observed after treated with PHI, but no effect on normal mononuclear cells. With the augmenting of time and dose,the expression of bcl-2, caspase-9,caspase-3,PRAP decreased. In contrast, alteration of caspase-8 was not significant. PHI can evidently inhibit the activity of the histone deacetylase and increased the histone acetyltransferase(HAT)P300 expression. It significantly induced the accumulation of acetylated histone H3; H4,and methylated H3k4.and decrease methylated H3K9.Conclusions PHI was able to inhibit the cell growth and decrease the viability of Molt-4 cells,induced apoptosis, arrest cell cycle at G0/G1.
Keywords/Search Tags:PHI, Histone, HAT, HDAC, HDACi, Epigenetics
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