Dataset Information

EGCG Inhibits Proliferation and Induces Apoptosis Through Downregulation of SIRT1 in Nasopharyngeal Carcinoma Cells.

ABSTRACT: Epigallocatechin-3-gallate (EGCG), a frequently studied catechin in green tea, has been shown involved in the anti-proliferation and apoptosis of human nasopharyngeal carcinoma (NPC) cells. However, the underlying molecular mechanism of the apoptotic effects of EGCG has not been fully investigated. Recent literature emphasized the importance of Sirtuin 1 (SIRT1), an NAD⁺-dependent protein deacetylase, in regulating cellular stress responses, survival, and organismal lifespan. Herein, the study showed that EGCG could significantly inhibit cell proliferation and promote apoptosis of 2 NPC (CNE-2 and 5-8F) cell lines. Moreover, it was also found that SIRT1 is down-regulated by EGCG, and the SIRT1-p53 signaling pathway participates in the effects of EGCG on CNE-2 and 5-8 F cells. Taken together, the findings of this study provided evidence that EGCG could inhibit the growth of NPC cell lines and is linked with the inhibition of the SIRT1-p53 signaling pathway, suggesting the therapeutic potential of EGCG in human NPC.

SUBMITTER: Jiang S

PROVIDER: S-EPMC9084317 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

EGCG Inhibits Proliferation and Induces Apoptosis Through Downregulation of SIRT1 in Nasopharyngeal Carcinoma Cells.

Jiang Shisheng S Huang Chaoming C Zheng Guodong G Yi Wei W Wu Bo B Tang Junyuan J Liu Xiawen X Huang Biyun B Wu Dan D Yan Tingdong T Li Mingxi M Wan Chunpeng C Cai Yi Y

Frontiers in nutrition 20220425

Epigallocatechin-3-gallate (EGCG), a frequently studied catechin in green tea, has been shown involved in the anti-proliferation and apoptosis of human nasopharyngeal carcinoma (NPC) cells. However, the underlying molecular mechanism of the apoptotic effects of EGCG has not been fully investigated. Recent literature emphasized the importance of Sirtuin 1 (SIRT1), an NAD<sup>+</sup>-dependent protein deacetylase, in regulating cellular stress responses, survival, and organismal lifespan. Herein, ...[more]

PMID: 35548580

Similar Datasets

Project description:Purpose: Recent studies indicate that pregnancy upregulated non-ubiquitous calmodulin kinase (PNCK) is significantly up-regulated in breast and renal carcinomas. However, the expression profile and its biological relevance of PNCK in nasopharyngeal carcinoma (NPC) have not been elucidated. Methods: The expression level of PNCK was detected in specimens of NPC (n=10) and normal tissues (n=10) by real-time PCR and immunohistochemistry. Celigo Cell Counting and MTT assay were used to measure cell viability. Apoptosis was detected by flow cytometric analysis and caspases 3/7 activity assay. Real-time PCR and Western blotting were performed to evaluate the expression of PNCK. The bioluminescence imaging was used to evaluate the effects of PNCK knockdown on tumor growth using a xenograft animal model. The global gene expression profile was determined in wild type and PNCK-depleted CNE-2 cells via transcriptomics analysis. For mechanical investigation, the changes of PI3K/AKT/mTOR signaling pathway were detected by Western blotting. Results: The mRNA and protein levels of PNCK were increased in human NPC samples. In vitro experiments showed that shRNA or CRISPR-Cas9 mediated silencing of PNCK inhibited proliferation and induced apoptosis in NPC cells. In addition, in vivo assay revealed that knockdown of PNCK suppressed tumor growth. Consistently, a significant reduction of tumor bioluminescence in mice inoculated with PNCK-knockdown cells compared to that of control cells. In gene expression, the transcriptomics analysis revealed that there were 589 upregulated genes and 589 downregulated genes in PNCK-knockdown cells. Ingenuity Pathway Analysis (IPA) identified significant changes of PI3K/AKT/mTOR signaling pathway in PNCK-knockdown cells. Furthermore, western blot analysis revealed that interference with PNCK reduced the phosphorylation levels of PI3K, AKT and mTOR in CNE-2 cells. Conclusion: This study for the first time demonstrates that knockdown of PNCK could suppress growth and induce apoptosis of NPC cells both in vitro and in vivo by regulating PI3K/AKT/mTOR signaling pathway. These findings suggest that PNCK might be a novel therapeutic target for NPC treatment.

Project description:The occurrence and development of hepatocellular carcinoma (HCC) are closely related to abnormal apoptosis. Brf1 is highly expressed in HCC and has clinical prognostic value. Here, attenuation of Brf1-induced apoptosis was found, and the related mechanism was explored. In the study, general bioinformatics data for Brf1 were obtained from The Human Protein Atlas (HPA). Analyses of the clinical prognostic value of Brf1 in HCC were performed with the Xiantao Academic web server using R software. The basic data were obtained from the GTEx database and TCGA database. Brf1 conditional knockout mice were obtained by repeated mating of C57BL/6 Brf1LoxP/LoxP and C57BL/6 NS5A-alb-Cre-ERT2 mice and verified by genotyping. Liver function measurements, hematoxylin and eosin staining (HE), and immunohistochemistry (IHC) were performed to explore the cause of mouse death after Brf1 knockout. The Brf1 knockdown HCC cell model was generated using lentiviral vector-based shRNA transduction. Cell proliferation assays, plate colony formation assays, anchorage-independent colony formation assays and mouse subcutaneous tumor models were used to evaluate the progression of HCC. Western blot (WB) analysis, flow cytometry, and TUNEL assays were used to detect apoptosis. DNA sequencing, transcriptomics, and proteomics analyses were carried out to explore the antiapoptotic mechanism of Brf1. We found that Brf1 was highly expressed in HCC and had clinical prognostic value. Brf1 knockout led to liver failure and hepatocyte apoptosis in mice. Downregulation of Brf1 slowed HCC cell proliferation, colony growth, and mouse subcutaneous tumor growth and increased the sensitivity of HCC cells to apoptosis induced by chemotherapy drugs. The expression of Brf1 was positively related to that of the apoptosis gene Bcl-2. The sequencing, transcriptomics and proteomics analyses consistently showed that energy metabolism played an important role in Brf1 function, that protein-protein interaction was the primary mode, and that organelles such as mitochondria were the main sites. In Conclusions, downregulation of Brf1 inhibits HCC development by inducing apoptosis. Energy metabolism plays an important role in Brf1 function. These results provide a scientific basis for combating HCC.

Dataset Information

EGCG Inhibits Proliferation and Induces Apoptosis Through Downregulation of SIRT1 in Nasopharyngeal Carcinoma Cells.

Publications

EGCG Inhibits Proliferation and Induces Apoptosis Through Downregulation of SIRT1 in Nasopharyngeal Carcinoma Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets