Genetic Alterations of DNA Methylation Machinery in Human Diseases

Hamidi, Tewfik; Singh, Anup K.; Chen, Taiping

doi:10.2217/epi.14.80

Cited by 212 publications

(157 citation statements)

References 116 publications

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“…9) DNMTs can catalyze Pcarelated gene nuclear factor-E2-related factor 2 (Nrf2) 10) and RASSF1A 11) methylation that promotes tumor progression. Gravina et al analyzed the correlation between ectopic expression of DNMT1, DNMT3a and DNMT3b and tumorigenic capacity of prostate cancer cells and concluded that the increased methylation in more aggressive tumors supporting the use of DNMTs in advanced prostate cancer.…”

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confidence: 99%

<i>Artesunate</i> Suppresses the Growth of Prostatic Cancer Cells through Inhibiting Androgen Receptor

Wang¹,

Wang²,

et al. 2017

Biological & Pharmaceutical Bulletin

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Prostatic cancer (PCa) is a leading cause of cancer related death in males and is often regarded as a kind of androgen-sensitive cancer. Artesunate (ART), a semi-synthetic derivative of the Chinese herb Artemisia annua, is such an anti-cancer agent. However, the effects and mechanism of ART on PCa cells remains unclear. The study aims to elaborate the mechanism of the involvement of androgen receptor (AR) in antiprostatic cancer (PCa) of artesunate (ART). PCa cells 22rvl were used in vivo and in vitro, and the viability and apoptosis were conducted using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay, respectively. Ectopic expressions of AR and DNA methyltransferase (DNMT) were detected in cells in overexpression or interference of AR or DNMT3b. ART dose-dependently suppressed tumor growth, inhibited cell viability, enhanced apoptosis, decreased AR expression, and increased the expression and the catalytic activity of DNMT3b in 22rv1 cells either in transplanted mice or in vitro. Furthermore, AR downregulated DNMT3b expression, and overexpression of AR or interference of DNMT3b could reverse ART-induced cytotoxicity and apoptosis in 22rvl cells, whereas overexpression of DNMT3b could not change the effect profiles of ART on the cells. The results indicated that ART suppressed tumor growth of prostatic cancer cells through AR-DNMT3b pathway, underlying ART will allow for the utilization of this Chinese therapeutic agent for the potential treatment of prostate cancer.Key words artesunate; prostatic cancer; androgen receptor; DNA methyltransferase; apoptosis Prostatic cancer (PCa) is the most common cause of cancerrelated death in males. Morbidity and mortality of PCa underscore the need for novel treatment options. Although improved therapies have been recently developed to treat and prevent PCa, prostate cancer still remains refractory disease. Lately, herbs and phytochemicals 1) have been attractive as therapeutic agents for tumorigenesis suppression. Understanding how the production of these Chinese herbs is regulated during cancer progression would help develop new cancer therapeutic strategy.Artesunate (ART) is a semi-synthetic derivative of artemisinin, the active principle of the Chinese herb Artemisia annua. ART has been revealed remarkable activity against otherwise multidrug-resistant Plasmodium falciparum and P. vivax malaria. With the recognition of ART, it has now been analyzed for its anti-cancer activity in various tissues-specificity. For example, Tran et al. found that enhancement of ART activity could effectively induce the apoptosis of breast cancer cells. 2)Moreover, ART was proved to be as a novel therapeutic agent for metastatic renal cell carcinoma due to its attenuation action on tumor growth, metastasis.3) Recently, Michaelsen et al. clinically treated PCa patients with long-term Artemisia annua capsules via oral administration combined with shortterm ART inj...

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confidence: 99%

<i>Artesunate</i> Suppresses the Growth of Prostatic Cancer Cells through Inhibiting Androgen Receptor

Wang¹,

Wang²,

et al. 2017

Biological & Pharmaceutical Bulletin

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“…A family of DNA methyltransferases transfer a methyl group from S-adenosyl methionine to the fifth carbon of a cytosine residue to form 5-methylcytosine, thereby catalyzing DNA methylation. This modification can be inherited through cell division (24). Beside its involvement in normal development in human beings, DNA methylation is frequently implicated in the onset or course of cancer due to its roles in many other regulatory processes.…”

Section: Discussionmentioning

confidence: 99%

Predictive value of gene methylation for second recurrence following surgical treatment of first bladder recurrence of a primary upper‑tract urothelial carcinoma

et al. 2018

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Abstract. The clinical relevance of aberrant DNA promoter methylation is being increasingly recognized in urothelial carcinoma. The present study was conducted to explore the methylation status of patients with upper-tract urothelial carcinoma (UTUC) who experienced bladder recurrence, and to evaluate the predictive value of gene methylation for second bladder recurrence and tumor progression. A total of 85 patients with primary UTUC, who experienced bladder recurrence after radical nephroureterectomy, were enrolled between January 2001 and December 2013. Using methylation-sensitive polymerase chain reaction, the promoter methylation statuses of 10 genes were analyzed in the bladder tumor specimens. Among the patient group, 32 patients experienced second bladder recurrence, and bladder progression was detected in 16. With the exception of BRCA1, the methylation rate of the majority of genes tended to gradually increase to varying extents with the number of recurrences; a smaller proportion of primary tumors exhibited gene methylation when compared with the first recurrent tumors and second recurrent tumors. Univariate and multivariate Cox regression analyses revealed that unmethylated GDF15 [hazard ratio (HR)=0.36; 95% confidence interval (CI), 0.14-0.92] and methylated VIM (HR=2.91; 95% CI, 1.11-7.61) in the first recurrent bladder tumor, as well as male gender (HR=2.28; 95% CI, 1.06-4.87), first recurrence interval <8 months (HR=2.34; 95% CI, 1.15-4.78) and primary UTUC tumor size ≥5 cm (HR=3.48; 95% CI, 1.43-8.45) were independent risk factors for a second bladder recurrence after surgery for the first bladder recurrence; the Harrell's concordance index (c-index) for the related nomogram was 0.71 (95% CI: 0.61-0.81). Furthermore, methylated CDH1 (HR=2.91; 95% CI, 1.08-7.77) and VIM (HR=4.91; 95% CI, 1.11-21.7) in the first recurrent bladder tumor, male gender (HR=3.6; 95% CI, 1.1-11.73), and primary tumor stage T2-T4 (HR=4.57; 95% CI, 1.22-17.13), multifocality (HR=3.64; 95% CI, 1.19-11.16) and size ≥5 cm (HR=3.1; 95% CI, 1.91-10.54) for the primary UTUC were considered to be predictors of tumor progression; the c-index for the nomogram was 0.88 (95% CI, 0.69-0.92). The present findings demonstrated that promoter methylation of cancer-related genes was frequently observed in patients with urothelial carcinoma, and that the gene methylation rate of certain genes tended to gradually increase with the number of bladder recurrences. This may be used as a predictive factor for a second bladder recurrence and tumor progression after the surgical treatment of the first bladder recurrence.

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“…5hmC is recognized poorly by Dnmt1 and can lead to replication-dependent passive demethylation. 5hmC can be further oxidized by Tet proteins to produce 5fC and 5caC [28] . Alternatively, 5hmC…”

Section: Dna Methylation Methods For the Specific Genelocus Specificmentioning

confidence: 99%

Epigenetic Modification of Ten Eleven Translocase Enzyme Mediated Hydroxymethylcytosine in Brain Derived Neurotrophic Factor for the Pathogenesis of Type II Diabetes Retinopathy

Tripathi¹

2017

JMSCR

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Genetic Alterations of DNA Methylation Machinery in Human Diseases

Cited by 212 publications

References 116 publications

<i>Artesunate</i> Suppresses the Growth of Prostatic Cancer Cells through Inhibiting Androgen Receptor

<i>Artesunate</i> Suppresses the Growth of Prostatic Cancer Cells through Inhibiting Androgen Receptor

Predictive value of gene methylation for second recurrence following surgical treatment of first bladder recurrence of a primary upper‑tract urothelial carcinoma

Epigenetic Modification of Ten Eleven Translocase Enzyme Mediated Hydroxymethylcytosine in Brain Derived Neurotrophic Factor for the Pathogenesis of Type II Diabetes Retinopathy

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