Effects of trichostatin A on FHIT and WWOX genes expression, cell growth inhibition and apoptosis induction in hepatocellular carcinoma WCH 17 cell line

Previously, we evaluated the effect of trichostatin A (TSA) on the expression of DNA methyltransferase 1 (DNMT1) in Hepatocellular Carcinoma (HCC). Fragile histidine triad (FHIT) and WW domaincontaining oxidoreductase (WWOX) are two of the most common down-regulated genes in many cancers located on chromosome 3p14.2 and 16q23.3–24.1 respectively. The aim of the current study was to assess the effect of TSA on these genes expression, cell growth, and apoptosis in HCC WCH 17 cell. The cells were seeded and treated with TSA at different times. Then, MTT assay, flow cytometry, and qRT-PCR were achieved to determine viability, apoptosis and gene expression respectively. Cell growth was significantly inhibited, 92 to 36% after 24 h, 86 to 28% after 48 h, and 78 to 24% after 72 h. The results of flow cytometry confirmed that TSA increased apoptosis compared to the control group, the apoptosis percentage increased to 12%, 16%, and 18% in comparison to control groups (2%). Significant up-regulation of the genes was observed in all treated groups. We concluded that reexpression of silenced WWOX and FHIT genes could be achieved by TSA resulting in cell growth inhibition and apoptosis induction in WCH 17 cell

The role of histone deacetylases in human gastrointestinal and associated glands cancer

Background & Objective: In the eukaryotic cells, the DNA wraps around the histone proteins (H2A, H2B, H3, and H4) and constitutes the nucleosome. Chromatin organization plays a major role in the control of gene expression. Epigenetic modifications can induce a reversible change in the chromatin structure as being open and accessible DNA to the transcriptional factors resulting in gene expression. Histone modification, as an epigenetic factor, is necessary for gene expression. These modifications are concluded in a balance between histone acetyltransferase and histone deacetylase activity. Histone deacetylation compacts chromatin structure resulting in gene silencing. Tumor suppressor genes play an important role in the cancer prevention. Deacetylation of these genes resulting in genes silencing and carcinogenesis. In this review, we will evaluate the effects of histone deacetylases on the gastroinetestinal tract and associated glands cancer. Methods: For this review article, we search different online sources by various researcher motors including Scopus, PubMed, and ISI resulted in finding articles correlated with the effect of histone deacetylase on the gastroinetestinal tract and associated glands cancer. Conclusions: In the current study, we concluded that histone deacetylases can induce cancer by histone deacetylation of tumor suppressor genes in the gastrointestinal tract and associated glands

Effect of genistein on apoptosis and proliferation of hepatocellular Carcinoma Hepa1-6 Cell Line

Background: One of the main causes of mortality is hepatocellular carcinoma (HCC) which accounts for the third leading cause of deaths and one in forty deaths worldwide. The flavonoids, natural antioxidant compounds, account for a major group of polyphenolic compounds. One of the major isoflavones in soybean is genistein (GE) which can inhibit proliferation and induce apoptosis. Isoflavones, major type of phenolic materials, derived from dietary plants and medicinal herbs play a significant role in cancer prevention and treatment. Correlation between dietary habits and cancer risk including breast, prostate, and colon cancer has been reported. Various bioactivities of these compounds such as anticarcinogenic and antioxidant are responsible for their chemopreventive activities by which induce migration, proliferation, cell cycle arrest, and apoptosis. GE, one of the major isoflavones, is considered as a potent chemopreventive agent against cancer. The aim of this study was to investigate the inhibitory and apoptotic effects of GE on HCC Hepa1-6 cell line. Methods: Cell viability assay and cell cycle analysis with flow cytometry were used to evaluate proliferative and apoptotic effect GE. Results: GE inhibited the growth of Hepa1-6 cells and induced apoptosis with a concentration and time-dependent fashion. During GE treatment for 24, the half maximal inhibitory concentration (IC50) was 20 μM, and the maximum inhibition of cell growth was 52% (P < 0.01). The percentage of apoptotic cells with a concentration of 20 μM of GE after 24, 48, and 72 h was 35, 42, and 65%, respectively (P < 0.01). Conclusions: Our finding clearly indicated that GE can significantly inhibit proliferation of hepatocellular carcinoma Hepa 1-6 cell line and induce apoptosis in this cell line

Effect of Genistein and 17-β Estradiol on the Viability and Apoptosis of Human Hepatocellular Carcinoma HepG2 cell line

Background: One of the most lethal cancers is hepatocellular carcinoma (HCC). Genistein (GE) is a choice compound for treatment of certain types of cancer. Phytoestrogens are plant derivatives that bear a structural similarity to 17-β estradiol (E2) and act in a similar manner. They are a group of lipophillic plant compounds with tumorigenic and antitumorigenic effects. E2 has stimulatory and inhibitory effects on cancer cell lines. This study was designed to investigate the antiproliferative and apoptotic effects of GE and E2 on the HCC HepG2 cell line. Materials and Methods: HepG2 cells were cultured and treated with various concentrations of GE and E2 and then 3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromideand flow cytometry assay were performed to determine cell viability and apoptosis. Results: GE and E2 induced apoptosis and inhibited cell growth significantly. Reduction of cell viability by 50% required 20 μM E2 for E2-treatment groups and 20 μMGE for GE-treatment groups. The percentage of the GE-treated apoptotic cells was reduced by about 35%, 42%, and 47% (P < 0.001) and that of E2-treated groups 34%, 39%, and 42% (P < 0.001) after 24, 48, and 72 h, respectively. Conclusions: Our experimental work clearly demonstrated that GE and E2 exhibited significant antiproliferative and apoptotic effects on human HCC HepG2 cells

Inhibitory effect of genistein on PLC/PRF5 hepatocellular carcinoma cell line

Background: Natural compounds including flavonoids like genistein (GE) are able to inhibit cell proliferation and induce apoptosis. GE is the main representative of these groups. GE inhibits carcinogenic tumors such as colon, stomach, lung, and pancreas tumors. The aim of the present study was to analyze the apoptotic effect of GE in the hepatocellular carcinoma (HCC) PLC/PRF5 cell line. Methods: Cells were treated with various doses of GE (1, 5, 10, 25, 50, 75, and 100 μM/L) at different times (24, 48, and 72 h) and the MTT assay was commonly used. Furthermore, cells were treated with single dose of GE (25 μM) at different times and flow cytometry was performed. Results: GE inhibited the growth of liver cancer cells significantly with a time- and dose-dependent manner. The percentage of living cells in GE treatment groups with a concentration of 25 μM at different times were 53, 48 and 47%, respectively (P < 0.001). Result of flow cytometry demonstrated that GE at a 25 μM concentration induces apoptosis significantly in a time-dependent manner. The percentage of apoptotic cells at different times were 44, 56, and 60%, respectively (P < 0.001). Conclusions: GE can significantly inhibit the growth of HCC cells and plays a significant role in apoptosis of this cell line