OBJECTIVETo investigate the effect of trichostatin A(TSA) on SGC- 7901 cells.

METHODSCytotoxicity and cell viability of gastric cancer cell line SGC- 7901 were assayed by MTT method. Morphologic assessment of apoptosis was performed with fluorescence microscope. Cell cycle and apoptosis rate were analyzed by flow cytometry. Histone H3 acetylation was detected by Western blot.

RESULTSTSA showed apparently cytotoxicity in SGC- 7901 cells. The growth curve showed the growth ratio decreased with the increase of TSA concentration. Apoptosis rate were significantly different between TSA treated group(75 ng/ml for 72 h)and control group (P < 0.05). Morphologic changes of apoptosis including nuclear chromatin condensation and fluorescence strength were observed with fluorescence microscope.TSA treatment (75 ng/ml for 72 h) sensitively induced apoptosis in the cell,which was demonstrated by the migration of many cells to the sub- G1 phase,the reduction of G1- phase cells and the increment of apoptosis rate (29.54%) in flow cytometric analysis. The expression of acetylated histone H3 was increased in TSA group(75 ng/ml) for 48 h compared with control group by Western blot.

CONCLUSIONSTSA can induce SGC- 7901 cell apoptosis. The expression of acetylated histone H3 may contribute to the apoptosis.

Acetylation ; drug effects ; Apoptosis ; drug effects ; Cell Line, Tumor ; Histones ; metabolism ; Humans ; Hydroxamic Acids ; pharmacology ; Stomach Neoplasms

OBJECTIVETo investigate the effects of PHI on histone acetylation and methylation in hepatocellular carcinoma line SMMC-7721 cells.

METHODSApoptosis was measured by TUNNEL assay. Histone methylation and acetylation were detected by Western blot.

RESULTSPHI inhibited cells growth and induced apoptosis. PHI treatment resulted in increased acetylation of histone H3 and H4 , elevated level of histone H3 lysine 4 methylation, and decreased level of histone H3 lysine 9 methylation.

CONCLUSIONSPHI can modulate both histone acetylation and methylation, which could remodel chromatin structure. PHI may be a novel anticancer drug.

Acetylation ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Histones ; metabolism ; Humans ; Isothiocyanates ; pharmacology ; Methylation

Some different membranes were prepared by Chitosan with the degree of deacetylation (DD) of 63.7%, 73.7%, 83% and 97% respectively. To study the biocompatibility of Chitosan membrane toward corneal stromal cells, the rabbit cells were cultured on the surface of different DD chitosan membranes. The morphological characteristics, the cell-adhesion, the cell proliferation and the activity of LDH in the medium were investigated. The results of experiment shows that the DD of Chitosan has very significant effect on the biocompatibility of Chitosan membrane toward corneal stromal cells. The more DD of Chitosan, the less injury was made to corneal stromal cells by the chitosan membrane, which is favor of the growing and adhesion of corneal stromal cells. The biocompatibility of the membrane made with low DD Chitosan with corneal stromal cells became worse.
Acetylation ; Animals ; Biocompatible Materials ; chemistry ; pharmacology ; Cell Adhesion ; drug effects ; Cell Division ; drug effects ; Chitosan ; chemistry ; pharmacology ; Cornea ; cytology ; Materials Testing ; Membranes, Artificial ; Rabbits ; Stromal Cells ; drug effects

This study investigated the inhibitory effects of curcumin on proliferation of hematological malignant cells in vitro and the anti-tumor mechanism at histone acetylation/histone deacetylation levels. The effects of curcumin and histone deacetylase inhibitor trichostatin A (TSA) on the growth of Raji cells were tested by MTT assay. The expression of acetylated histone-3 (H(3)) in Raji, HL60 and K562 cells, and peripheral blood mononuclear cells (PBMCs) treated with curcumin or TSA was detected by immunohistochemistry and FACS. The results showed curcumin inhibited proliferation of Raji cells significantly in a time- and dose-dependent fashion, while exhibited low toxicity in PBMCs. Curcumin induced up-regulation of the expression of acetylated H(3) dose-dependently in all malignant cell lines tested. In conclusion, curcumin inhibited proliferation of Raji cells selectively, enhanced the level of acetylated (H(3)) in Raji, HL60, and K562 cells, which acted as a histone deacetylase inhibitor like TSA. Furthermore, up-regulation of H(3) acetylation may play an important role in regulating the proliferation of Raji cells.
Acetylation/drug effects ; Antineoplastic Agents/*pharmacology ; Cell Proliferation/*drug effects ; Curcumin/*pharmacology ; HL-60 Cells ; Histone Deacetylase Inhibitors/pharmacology ; Histones/chemistry ; Histones/*drug effects ; K562 Cells ; Triclosan/pharmacology

In order to examine the strong anticancer action and low toxicity of Trichostatin A (TSA), the effect of TSA was examined on the growth inhibition, acetylation of histone H3 and apoptosis in HL-60 cells by employing MTT, immunocytochemical techniques, and Annexin-V-FITC/ PI assay. Our results showed that TSA could inhibit proliferation of HL- 60 cells in a time- and dose-dependent manner, and the IC50 at the 36th h was 100 ng/ml. The apoptosis-inducing effect of TSA on HL-60 cells was also time- and dose-dependent. But it didn't demonstrate apparent apoptosis induction in NPBMNCs within specific dose and time range. Both of the acetylation of histone H3 in HL-60 cells and NPBMNCs increased significantly (P<0.05) after treated with 100 ng/ml TSA for 4 h. However, there was no significant differences between the two groups (P>0.05). It is concluded that TSA can inhibit growth and induce apoptosis of HL-60 cells in a time- and dose-dependent manner, and is able to selectively induce apoptosis in HL-60 cells but does not respond in NPBMNCs under the same conditions. The difference of TSA between HL-60 cells and NPBMNCs can't be explained by the regulation of histone acetylation.
Acetylation ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; HL-60 Cells ; Histone Deacetylase Inhibitors ; Histone Deacetylases ; chemistry ; Humans ; Hydroxamic Acids ; pharmacology

In order to examine the strong anticancer action and low toxicity of Trichostatin A (TSA), the effect of TSA was examined on the growth inhibition, acetylation of histone H3 and apoptosis in HL-60 cells by employing MTT, immunocytochemical techniques, and Annexin-V-FITC/ PI assay. Our results showed that TSA could inhibit proliferation of HL- 60 cells in a time- and dose-dependent manner, and the IC50 at the 36th h was 100 ng/ml. The apoptosis-inducing effect of TSA on HL-60 cells was also time- and dose-dependent. But it didn't demonstrate apparent apoptosis induction in NPBMNCs within specific dose and time range. Both of the acetylation of histone H3 in HL-60 cells and NPBMNCs increased significantly (P<0.05) after treated with 100 ng/ml TSA for 4 h. However, there was no significant differences between the two groups (P>0.05). It is concluded that TSA can inhibit growth and induce apoptosis of HL-60 cells in a time- and dose-dependent manner, and is able to selectively induce apoptosis in HL-60 cells but does not respond in NPBMNCs under the same conditions. The difference of TSA between HL-60 cells and NPBMNCs can't be explained by the regulation of histone acetylation.
Acetylation ; Antineoplastic Agents/pharmacology ; Apoptosis/*drug effects ; HL-60 Cells ; Histone Deacetylases/antagonists & inhibitors ; Histone Deacetylases/*chemistry ; Hydroxamic Acids/*pharmacology

This study was purposed to investigate the effects of phenylhexyl isothiocyanate (PHI) on Burkitt lymphoma Daudi cell line and regulation of histone acetylation and methylation in Daudi cells, and to explore the potential mechanism. The apoptotic rate of Daudi cells treated with PHI was measured by flow cytometry, the changes of histone H3 and H4 acetylation, histone H3K9 and H3K4 methylation in Daudi cells treated with PHI were detected by Western blot. The results showed that PHI could induce apoptosis of Daudi cells, increased the acetylation level of H3 and H4, enhanced the methylation of H3K4, but reduced the methylation of H3K9. It is concluded that the PHI can up-regulate the acetylation level of histone H3 associated with transcription stimulation and the methylation of histone H3K4, down-regulate the methylation on histone H3K9 associated with transcription inhibition, promotes the apoptosis of Daudi cells. PHI may be a potential agent for target therapy of lymphoma.
Acetylation ; Apoptosis ; drug effects ; Burkitt Lymphoma ; genetics ; metabolism ; Cell Line, Tumor ; Histones ; genetics ; metabolism ; Humans ; Isothiocyanates ; pharmacology ; Methylation

There are large knowledge gaps regarding how to control stem cells growth and differentiation. The limitations of currently available technologies, such as growth factors and/or gene therapies has led to the search of alternatives. We explore here how a cell's epigenome influences determination of cell type, and potential applications in tissue engineering. A prevalent epigenetic modification is the acetylation of DNA core histone proteins. Acetylation levels heavily influence gene transcription. Histone deacetylase (HDAC) enzymes can remove these acetyl groups, leading to the formation of a condensed and more transcriptionally silenced chromatin. Histone deacetylase inhibitors (HDACis) can inhibit these enzymes, resulting in the increased acetylation of histones, thereby affecting gene expression. There is strong evidence to suggest that HDACis can be utilised in stem cell therapies and tissue engineering, potentially providing novel tools to control stem cell fate. This review introduces the structure/function of HDAC enzymes and their links to different tissue types (specifically bone, cardiac, neural tissues), including the history, current status and future perspectives of using HDACis for stem cell research and tissue engineering, with particular attention paid to how different HDAC isoforms may be integral to this field.
Acetylation ; drug effects ; Histone Deacetylase Inhibitors ; pharmacology ; Histone Deacetylases ; metabolism ; Histones ; isolation & purification ; metabolism ; Humans ; Tissue Engineering

OBJECTIVETo investigate the effect of phenyl-hexyl isothiocyanate (PHI) on acetylation and methylation of histone in acute lymphoblastic leukemia cell line Molt4.

METHODSThe inhibition of cell proliferation was observed by MTT method and clone suppression test. Apoptosis and cell cycle arrest were measured by flow cytometry. The alterations in histone acetyltransferase and acetylation and methylation of histones were detected by Western blot.

RESULTSPHI could up-regulate the expression of acetyltransferase (P300/CBP), markedly induced the accumulation of acetylated histone H3, H4 and methylated histone H3 lysine 4 (H3K4), and inhibited methylation on lysine 9 of H3 (H3K9). The epigenetic regulation resulted in cell cycle arrest at G0/G1 phase, and induction of apoptosis.

CONCLUSIONSPHI can modulate both histone methylation and acetylation. It may serve as a histone deacetylase inhibitor, and might be a potential novel anti-leukemia agent.

Acetylation ; drug effects ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Epigenesis, Genetic ; Histone Deacetylases ; metabolism ; Histones ; metabolism ; Humans ; Isothiocyanates ; pharmacology ; Methylation ; drug effects

OBJECTIVETo investigate the effects of curcumin on the acetylation of histone H3, P53 and the proliferation of NB4 cells.

METHODSThe total protein was extracted from NB4 cells treated without or with different concentrations of curcumin ( 50, 25, 12.5, 6.25 and 3.125 micromol/L) for different time (0, 4, 8, 12, 24 h). Western blot analysis was performed to determine the levels of acetylated histone H3, P53 and acetylated P53. MTT assay was performed to examine the growth inhibition effect of curcumin on NB4 cells.

RESULTSCurcumin could inhibit the proliferation of NB4 cells in a time- and dose- dependent manner, with the IC50 at 24 h and 36 h of 40 micromol/L and 25 micromol/L, respectively. The levels of histone H3 acetylation, P53 expression and P53 acetylation were increased obviously.

CONCLUSIONCurcumin functions as a deacetylase inhibitor,which could increase the level of acetylated histone H3, enhance the expression and activity of tumor suppressor P53, and inhibit the proliferation of NB4 cells.

Acetylation ; drug effects ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Curcumin ; pharmacology ; Histones ; metabolism ; Humans ; Tumor Suppressor Protein p53 ; metabolism