RESUMO
Objective To observe the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and to investigate the epigenetic regulation of EZH2 inhibitor DZNeP on osteogenic differentiation of hPDLSCs. Methods The hPDLSCs were isolated and cultured, and their proliferation under different concentrations of DZNeP (0, 1, 2, 5 and 10 μmol/L) was detected by MTT. The effects of DZNeP on osteogenic differentiation of hPDLSCs were observed by alkaline phosphatase (ALP) staining and alizarin red staining. The effect of DZNeP on the trimethylation of histone H3K27 in hPDLSCs was detected by immunofluorescence staining. Results Compared with the control group, the proliferation of hPDLSCs after 1, 2, 5 and 10 μmol/L DZNeP treatment for 48 h was significantly decreased, respectively (all P<0.05), and it was concentration-dependent. The result of ALP staining and alizarin red staining showed that DZNeP could promote the expression of early osteogenic markers ALP and the formation of advanced calcified nodules of hPDLSCs. The immunofluorescence staining result showed that the trimethylation fluorescence intensity of histone H3K27 was significantly decreased in the DZNeP group compared with the control group. Conclusions As an EZH2 inhibitor, DZNeP can inhibit the proliferation of hPDLSCs and promote the differentiation of hPDLSCs into osteoblasts in vitro, suggesting that DZNeP can be used as a potential small molecule drug for the treatment of periodontitis.
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Objective To study the effects of S-adenosyl-homocysteine hydrolase inhibitor DZNep (3-Dea zaneplanocin A) on human prostatic cancer PC3 cells growth and further explore its potential value in anti-human prostatic cancer treatment.Methods MTT method was used to analyze the effects of EZH2 gene silencing,EZH2 over-expression and DZNep treatment on cell proliferation.Gene expression of EZH2,Bax and Bcl-2 in PC3 cells was detected with western blot.Results DZNep could significantly inhibit PC3 cell growth and induce apoptosis which was identified with Bax expression up-regulation and Bcl-2 expression down-regulation.EZH2 knock-down inhibited PC3 cells growth,and over-expression of EZH2 partially counteract the inhibitory effects of DZNep on PC3 cells growth.Conclusions DZNep can inhibit PC3 cells growth by targeting EZH2 inhibition which leads to endogenous apoptosis.DZNep has the potential value in the treatment of human prostatic cancer.
RESUMO
Enhancer of zeste homolog 2 (EZH 2) is considered to be a novel oncogene in recent years. 3-Deazaneplanocin A (DZNep, an inhibitor of EZH2), has been intensively focused for its effect upon cancers by exerting potential anti-proliferative and pro-apoptotic effects via blocking the EZH2 pathway. As a new chromatin modification drug, growing evidence suggests that DZNep is involved in pathophysiological process of tumor cells, such as proliferation, apoptosis, invasion, metastasis and vascularization. DZNep may provide a new approach for the treatment of tumors. This review summarizes the research progress in DZNep in tumor therapy.
RESUMO
EZH2 is over-expressed in human colon cancer and is closely associated with tumor proliferation, metastasis and poor prognosis. Targeting and inhibiting EZH2 may be an effective therapeutic strategy for colon cancer. 3-Deazaneplanocin A (DZNep), as an EZH2 inhibitor, can suppress cancer cell growth. However, the anti-cancer role of DZNep in colon cancer cells has been rarely studied. In this study, we demonstrate that DZNep can inhibit the growth and survival of colon cancer HCT116 cells by inducing cellular senescence and apoptosis. The study provides a novel view of anti-cancer mechanisms of DZNep in human colon cancer cells.