Curcumin from Turmeric Rhizome: A Potential Modulator of DNA Methylation Machinery in Breast Cancer Inhibition

One of the most systematically studied bioactive nutraceuticals for its benefits in the management of various diseases is the turmeric-derived compounds: curcumin. Turmeric obtained from the rhizome of a perennial herb Curcuma longa L. is a condiment commonly used in our diet. Curcumin is well known for its potential role in inhibiting cancer by targeting epigenetic machinery, with DNA methylation at the forefront. The dynamic DNA methylation processes serve as an adaptive mechanism to a wide variety of environmental factors, including diet. Every healthy tissue has a precise DNA methylation pattern that changes during cancer development, forming a cancer-specific design. Hypermethylation of tumor suppressor genes, global DNA demethylation, and promoter hypomethylation of oncogenes and prometastatic genes are hallmarks of nearly all types of cancer, including breast cancer. Curcumin has been shown to modulate epigenetic events that are dysregulated in cancer cells and possess the potential to prevent cancer or enhance the effects of conventional anti-cancer therapy. Although mechanisms underlying curcumin-mediated changes in the epigenome remain to be fully elucidated, the mode of action targeting both hypermethylated and hypomethylated genes in cancer is promising for cancer chemoprevention. This review provides a comprehensive discussion of potential epigenetic mechanisms of curcumin in reversing altered patterns of DNA methylation in breast cancer that is the most commonly diagnosed cancer and the leading cause of cancer death among females worldwide. Insight into the other bioactive components of turmeric rhizome as potential epigenetic modifiers has been indicated as well.

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In silico study of cancer stage-specific DNA methylation pattern in White breast cancer patients based on TCGA dataset

Computational Biology and Chemistry ◽

10.1016/j.compbiolchem.2021.107498 ◽

2021 ◽

Vol 92 ◽

pp. 107498

Author(s):

Jeremias Ivan ◽

Gabriella Patricia ◽

David Agustriawan

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Cancer Patients ◽

In Silico ◽

Methylation Pattern ◽

Cancer Stage ◽

Breast Cancer Patients ◽

In Silico Study ◽

Dna Methylation Pattern ◽

Tcga Dataset

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Serum/plasma DNA methylation pattern and early detection of breast cancer

Clinical Cancer Investigation Journal ◽

10.4103/2278-0513.152715 ◽

2015 ◽

Vol 4 (2) ◽

pp. 120

Author(s):

AliM Ardekani ◽

Hamed Abdolghafoorian ◽

Arootin Gharibiyan ◽

SeyedAhmad Hashemi ◽

Mahdie Hadi

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Early Detection ◽

Methylation Pattern ◽

Plasma Dna ◽

Dna Methylation Pattern

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Oxidative DNA Damage Modulates DNA Methylation Pattern in Human Breast Cancer 1 (BRCA1) Gene via the Crosstalk between DNA Polymerase β and a de novo DNA Methyltransferase

Cells ◽

10.3390/cells9010225 ◽

2020 ◽

Vol 9 (1) ◽

pp. 225 ◽

Cited By ~ 2

Author(s):

Zhongliang Jiang ◽

Yanhao Lai ◽

Jill M. Beaver ◽

Pawlos S. Tsegay ◽

Ming-Lang Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Dna Damage ◽

Dna Polymerase ◽

Dna Methyltransferase ◽

Oxidative Dna Damage ◽

De Novo ◽

Brca1 Gene ◽

Methylation Pattern ◽

Dna Polymerase Β

DNA damage and base excision repair (BER) are actively involved in the modulation of DNA methylation and demethylation. However, the underlying molecular mechanisms remain unclear. In this study, we seek to understand the mechanisms by exploring the effects of oxidative DNA damage on the DNA methylation pattern of the tumor suppressor breast cancer 1 (BRCA1) gene in the human embryonic kidney (HEK) HEK293H cells. We found that oxidative DNA damage simultaneously induced DNA demethylation and generation of new methylation sites at the CpGs located at the promoter and transcribed regions of the gene ranging from −189 to +27 in human cells. We demonstrated that DNA damage-induced demethylation was mediated by nucleotide misincorporation by DNA polymerase β (pol β). Surprisingly, we found that the generation of new DNA methylation sites was mediated by coordination between pol β and the de novo DNA methyltransferase, DNA methyltransferase 3b (DNMT3b), through the interaction between the two enzymes in the promoter and encoding regions of the BRCA1 gene. Our study provides the first evidence that oxidative DNA damage can cause dynamic changes in DNA methylation in the BRCA1 gene through the crosstalk between BER and de novo DNA methylation.

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Vernalization-induced changes of the DNA methylation pattern in winter wheat

Genome ◽

10.1139/g01-147 ◽

2002 ◽

Vol 45 (2) ◽

pp. 253-260 ◽

Cited By ~ 55

Author(s):

Jamie D Sherman ◽

Luther E Talbert

Keyword(s):

Dna Methylation ◽

Winter Wheat ◽

Spring Wheat ◽

Cold Treatment ◽

Methylation Pattern ◽

Dna Demethylation ◽

Near Isogenic Lines ◽

Length Polymorphisms ◽

Amplified Fragment Length Polymorphisms ◽

Induced Changes

Vernalization is a cold treatment that induces or accelerates flowering and insures that temperate-zone plants will not flower until after winter. There is evidence that vernalization results in DNA demethylation that induces flowering. Differences in DNA methylation can be determined using methylation-sensitive amplified fragment length polymorphisms (AFLPs). Methylation-sensitive AFLPs utilize restriction enzyme isoschizomers that are differentially sensitive to methylation, producing polymorphisms related to methylation differences as opposed to sequence differences. Near-isogenic lines (NILs) have been developed for spring vs. winter habit in wheat (Triticum aestivum) and allow for the study of a single vernalization locus. In this study, differences in the methylation pattern were determined for spring and winter NILs, as well as for unvernalized and vernalized individuals. Winter wheat was more highly methylated than spring wheat and methylation-related AFLPs were produced between winter and spring wheat. Changes in the methylation pattern were observed at the end of vernalization, one week after the end of vernalization, and four weeks after the end of vernalization of winter wheat. However, the most methylation differences were observed one week after removal of winter wheat from cold treatment. Our data suggest that there is not only a vernalization-induced demethylation related to flower induction, but there is also a more general and non-specific demethylation of sequences unrelated to flowering. Two methylation-related AFLPs induced by vernalization were shared among all of the winter NILs.Key words: vernalization, wheat, DNA demethylation, AFLP.

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Obesity and menopause modify the epigenomic profile of breast cancer

Endocrine Related Cancer ◽

10.1530/erc-16-0565 ◽

2017 ◽

pp. 351-363 ◽

Cited By ~ 16

Author(s):

Ana B Crujeiras ◽

Angel Diaz-Lagares ◽

Olafur A Stefansson ◽

Manuel Macias-Gonzalez ◽

Juan Sandoval ◽

...

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

High Risk ◽

Risk Group ◽

Menopausal Status ◽

Breast Tumors ◽

Methylation Pattern ◽

High Risk Group ◽

Cpg Sites ◽

The Impact

Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes. Data from Infinium 450K array-based methylomes of 64 breast tumors were coupled with information on BMI and menopausal status. Additionally, DNA methylation results were validated in 18 non-tumor and 81 tumor breast samples. Breast tumors arising in either pre- or postmenopausal women stratified by BMI or menopausal status alone were not associated with a specific DNA methylation pattern. Intriguingly, the DNA methylation pattern identified in association with the high-risk group (postmenopausal women with high BMI (>25) and premenopausal women with normal or low BMI < 25) exclusively characterized by hypermethylation of 1287 CpG sites as compared with the low-risk group. These CpG sites included the promoter region of fourteen protein-coding genes of which CpG methylation over the ZNF577 promoter region represents the top scoring associated event. In an independent cohort, the ZNF577 promoter methylation remained statistically significant in association with the high-risk group. Additionally, the impact of ZNF577 promoter methylation on mRNA expression levels was demonstrated in breast cancer cell lines after treatment with a demethylating agent (5-azacytidine). In conclusion, the epigenome of breast tumors is affected by a complex interaction between BMI and menopausal status. The ZNF577 methylation quantification is clearly relevant for the development of novel biomarkers of precision therapy in breast cancer.

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DNA methylation pattern of theSLC25A43gene in breast cancer

Epigenetics ◽

10.4161/epi.7.3.19064 ◽

2012 ◽

Vol 7 (3) ◽

pp. 300-306 ◽

Cited By ~ 9

Author(s):

Breezy Malakkaran Lindqvist ◽

Sanja A. Farkas ◽

Sten Wingren ◽

Torbjörn K. Nilsson

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Methylation Pattern ◽

Dna Methylation Pattern

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Diagnostic values of GHSR DNA methylation pattern in breast cancer

Breast Cancer Research and Treatment ◽

10.1007/s10549-012-2197-z ◽

2012 ◽

Vol 135 (3) ◽

pp. 705-713 ◽

Cited By ~ 13

Author(s):

Sandeep Kumar Botla ◽

Amin Moghaddas Gholami ◽

Mahdi Malekpour ◽

Evgeny A. Moskalev ◽

Mahdi Fallah ◽

...

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Methylation Pattern ◽

Diagnostic Values ◽

Dna Methylation Pattern

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Epigenetic machinery is functionally conserved in cephalopods

10.1101/2021.11.18.469068 ◽

2021 ◽

Author(s):

Filippo Macchi ◽

Eric Edsinger ◽

Kirsten C Sadler

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Methylation Pattern ◽

Model Organisms ◽

Specific Gene ◽

Molecular Approaches ◽

Maintenance Factors ◽

Epigenetic Machinery ◽

Static Pattern ◽

Identify Gene Expression

Epigenetic regulatory mechanisms are divergent across the animal kingdom, yet little is known about the epigenome in non-model organisms. Unique features of cephalopods make them attractive for investigating behavioral, sensory, developmental and regenerative processes, but using molecular approaches in such studies is hindered by the lack of knowledge about genome organization and gene regulation in these animals. We combined bioinformatic and molecular analysis of Octopus bimaculoides to identify gene expression signatures for 12 adult tissues and a hatchling, and investigate the presence and pattern of DNA methylation and histone methylation marks across tissues. This revealed a dynamic gene expression profile encoding several epigenetic regulators, including DNA methylation maintenance factors that were highly conserved and functional in cephalopods, as shown by detection of 5-methyl-cytosine in multiple tissues of octopus, squid and bobtail squid. WGBS of octopus brain and RRBS from a hatchling revealed that less than 10% of CpGs are methylated, highlighting a non-random distribution in the genome of all tissues, with enrichment in the bodies of a subset of 14,000 genes and absence from transposons. Each DNA methylation pattern encompassed genes with distinct functions and, strikingly, many of these genes showed similar expression levels across tissues. In contrast to the static pattern of DNA methylation, the histone marks H3K27me3, H3K9me3 and H3K4me3 were detected at different levels in diverse cephalopod tissues. This suggests the methylome and histone code cooperate to regulate tissue specific gene expression in a way that may be unique to cephalopods.

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