Effects of green tea polyphenol on methylation status of RECK gene and cancer cell invasion in oral squamous cell carcinoma cells

Kato, Kazúo; Long, Nguyen Khanh; Makita, Hiroki; Toida, Makoto; Yamashita, Tomomi; Hatakeyama, Daijiro; Hara, Akira; Mori, Hideki; Shibata, Toshiyuki

doi:10.1038/sj.bjc.6604521

Cited by 170 publications

(116 citation statements)

References 34 publications

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“…Gene promoter hypermethyla tion has been associated with the silencing of tumor-related genes, which is considered the most important epigenetic dis ruption in numerous tumors (18,19). In a previous study, hypermethylation of the RECK gene was partially reversed by epigallocatechin gallate treatment, and the mRNA expression level of RECK was significantly enhanced in oral squamous cell carcinoma cell lines (20). RAS was able to increase the binding of DNA methyltransferase (DNMT) 3B to the RECK promoter and induce promoter methylation, while treatment with 5'-azacytidine and DNMT3B-targeting siRNA restored RECK expression and potently suppressed cell invasion (21).…”

Section: Introductionmentioning

confidence: 98%

Promoter hypermethylation of the RECK gene is associated with its low expression and poor survival of esophageal squamous cell carcinoma

Zhu

Yang

et al. 2017

Oncology Letters

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Abstract. The present study aimed to investigate the association between the methylation status of the reversion-inducing cysteine-rich protein with kazal motifs (RECK) gene and its mRNA expression levels in patients with esophageal squamous cell carcinoma (ESCC). The methylation status of RECK was analyzed by methylation-specific polymerase chain reaction (PCR), and RECK mRNA expression levels were analyzed by quantitative PCR, in 310 paired ESCC tissues. The mean RECK methylation index (MI) was 0.65 in ESCCs and 0.49 in non-tumor samples. There was a significant association between RECK methylation and the American Joint Committee on Cancer stage and lymph node metastasis in ESCC (P<0.0001; P=0.001). The mRNA expression level of RECK was lower in ESCC tissues (mean -∆Cq =-4.66) compared with non-tumor tissues (mean -∆Cq =-2.79), and decreased RECK mRNA expression levels were associated with lymph node metastasis in ESCC. In addition, RECK mRNA levels were decreased in ESCC patients with hypermethylation of the RECK gene (∆MI >0.16; mean -∆∆Cq =-2.85) compared with those with hypomethylation of the RECK gene (∆MI ≤0.16; mean -∆∆Ct =-0.83), and there was a significant difference in the mRNA expression levels of RECK between those with N 0-1 and N 2-3 lymph node metastasis (P<0.0001). A significant correlation was observed between RECK mRNA expression levels, the MI of RECK and poor postoperative survival (P=0.0003; P<0.0001). The results of the present study suggested that promoter hypermethylation may be an important factor for loss of RECK mRNA expression and may be an indicator of poor survival in ESCC.

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Section: Introductionmentioning

confidence: 98%

Promoter hypermethylation of the RECK gene is associated with its low expression and poor survival of esophageal squamous cell carcinoma

Zhu

Yang

et al. 2017

Oncology Letters

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“…EGCG is a major polyphenol in green tea, and a key active ingredient (19). Previous studies (24,25) have demonstrated that EGCG inhibits DNMT and inhibits the hypermethylation of newly synthesised DNA, resulting in the reversal of hypermethylation and the re-expression of silenced genes, with fewer side effects and toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…To determine the dose-and time-dependent changes associated with EGCG treatment, the SACC83 cells were treated in triplicate with EGCG (Wako Pure Chemical Industries, Ltd., Osaka, Japan), as described previously (19). Briefly, the cells were seeded at low density (5x10 5 /100 mm dish) 24 h prior to treatment with EGCG.…”

Section: Introductionmentioning

confidence: 99%

Epigallocatechin-3-gallate inhibits the invasion of salivary adenoid cystic carcinoma cells by reversing the hypermethylation status of the RECK gene

Zhou

et al. 2015

Molecular Medicine Reports

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Abstract. Epigallocatechin-3-gallate (EGCG) is an active and major constituent of green tea. As a non-nucleoside inhibitor of DNA methylation, EGCG is able to inhibit the hypermethylation of newly synthesised DNA, resulting in the reversal of hypermethylation and recovery in expression of the silenced genes. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a novel tumour suppressor gene, which negatively regulates matrix metalloproteinases, and inhibits tumour invasion, angiogenesis and metastasis. The present study aimed to examine the effects of EGCG on the methylation status of the RECK gene and tumour invasion in a salivary adenoid cystic carcinoma (SACC) cell line in vitro. Marked levels of methylated and weak levels of unmethylated RECK promoter were detected in the SACC83 cells, which was determined using methylation-specific polymerase chain reaction (PCR). In addition, the treatment of SACC83 cells with EGCG partially reversed the hypermethylation status of the RECK gene. Western blot analysis and reverse transcription-PCR demonstrated that EGCG significantly enhanced the protein and mRNA expression levels of RECK, and significantly reduced the invasive ability of the SACC83 cells, as determined using a Transwell assay. These results suggested that EGCG possesses novel anti-metastatic therapeutic potential for the treatment of SACC. IntroductionSalivary adenoid cystic carcinoma (SACC) is one of the most common types of malignancy, which is known to be associated with persistent slow growth, perineural invasion, high rates of recurrence and the formation of distant metastases (1). Despite the use of aggressive surgery, the 5-year survival rate of SACC is ~75%, whereas the long-term survival rate is only 39.6% (2). The underlying molecular mechanisms of SACC carcinogenesis remain to be fully elucidated.Changes in DNA methylation is commonly observed in human cancer (3,4). The hypomethylation of oncogenes can result in their aberrant activation, and hypermethylation of tumour suppressor genes can result in their silencing (5). DNA methylation inhibitors can be divided into two categories: Nucleoside inhibitors and non-nucleoside inhibitors. Nucleoside inhibitors, including 5-aza-2'-deoxycytidine, are associated with substantial toxic effects and have short half-lives in aqueous solutions (6). Epigallocatechin-3-gallate (EGCG) is a non-nucleoside inhibitor (7), which mediates the inhibition of DNA methylation by binding to the catalytic pocket of human DNA methyltransferase (DNMT) and inhibit the hypermethylation of newly synthesised DNA, resulting in the reversal of hypermethylation and the re-expression of silenced genes.Several oncogene and tumour suppressor gene candidates have been suggested to be involved in SACC, including suprabasin (8), aquaporin 1 (9), phosphatase and tensin homolog deleted on chromosome 10 (10), cyclin-dependent kinase inhibitors (11) and RAS-associated domain family protein 1A (12). The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) gene is...

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“…RECK activity is down-regulated in several human cancers and is associated with promoter hypermethylation in the gene. In an elegant study, Kato et al (23) investigated how EGCG altered RECK DNA methylation and expression in four human oral squamous cell carcinoma cell lines. Critically, they investigated whether reversing hypermethylation and increasing RECK gene expression could inhibit oral squamous cell carcinoma migration and invasiveness.…”

Section: Epigenetics Diet and Diseasementioning

confidence: 99%

Epigenetic modifications and human pathologies: cancer and CVD

Duthie

2010

Proc. Nutr. Soc.

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Epigenetic changes are inherited alterations in DNA that affect gene expression and function without altering the DNA sequence. DNA methylation is one epigenetic process implicated in human disease that is influenced by diet. DNA methylation involves addition of a 1-C moiety to cytosine groups in DNA. Methylated genes are not transcribed or are transcribed at a reduced rate. Global under-methylation (hypomethylation) and site-specific over-methylation (hypermethylation) are common features of human tumours. DNA hypomethylation, leading to increased expression of specific proto-oncogenes (e.g. genes involved in proliferation or metastasis) can increase the risk of cancer as can hypermethylation and reduced expression of tumour suppressor (TS) genes (e.g. DNA repair genes). DNA methyltransferases (DNMT), together with the methyl donor S-adenosylmethionine (SAM), facilitate DNA methylation. Abnormal DNA methylation is implicated not only in the development of human cancer but also in CVD. Polyphenols, a group of phytochemicals consumed in significant amounts in the human diet, effect risk of cancer. Flavonoids from tea, soft fruits and soya are potent inhibitors of DNMT in vitro, capable of reversing hypermethylation and reactivating TS genes. Folates, a group of water-soluble B vitamins found in high concentration in green leafy vegetables, regulate DNA methylation through their ability to generate SAM. People who habitually consume the lowest level of folate or with the lowest blood folate concentrations have a significantly increased risk of developing several cancers and CVD. This review describes how flavonoids and folates in the human diet alter DNA methylation and may modify the risk of human colon cancer and CVD.

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Effects of green tea polyphenol on methylation status of RECK gene and cancer cell invasion in oral squamous cell carcinoma cells

Cited by 170 publications

References 34 publications

Promoter hypermethylation of the RECK gene is associated with its low expression and poor survival of esophageal squamous cell carcinoma

Promoter hypermethylation of the RECK gene is associated with its low expression and poor survival of esophageal squamous cell carcinoma

Epigallocatechin-3-gallate inhibits the invasion of salivary adenoid cystic carcinoma cells by reversing the hypermethylation status of the RECK gene

Epigenetic modifications and human pathologies: cancer and CVD

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