Genistein inhibits DNA methylation and increases expression of tumor suppressor genes in human breast cancer cells

Xie, Qiang; Bai, Qian; Zou, Lingyun; Zhang, Qianyong; Zhou, Yong; Chang, Hui; Lv, Yi; Zhu, Jingjing; Mi, Mantian

doi:10.1002/gcc.22154

Cited by 171 publications

(127 citation statements)

References 39 publications

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“…Isoflavones (especially genistein) have been shown to induce epigenetic modifications [18,19,20]. To test whether dietary introduction of isoflavones will induce epigenetic modifications of promoter sites of IL-4, we tested the demethylation of specific CpG sequences in 2 sites of the IL-4 promoter region in mouse splenocytes and mesenteric lymph node cells by pyrosequencing (online suppl.…”

Section: Resultsmentioning

confidence: 99%

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Dietary Elimination of Soybean Components Enhances Allergic Immune Response to Peanuts in BALB/c Mice

Chang¹,

Song²,

Li³

et al. 2015

Int Arch Allergy Immunol

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Background: Food allergy research is hampered by a lack of animal models that consistently mimic human food allergic responses. Laboratory mice are generally fed grain-based chow made with large amounts of soybeans rich in immunomodulatory isoflavones. We tested the role of dietary soy components in the induction of food allergic responses in the BALB/c mouse strain, which is known to be resistant to anaphylaxis when orally challenged by food allergens. Methods: Mice were fed a soy-free diet for 2 generations. After weaning, mice were maintained on the same diet or fed a diet containing soy isoflavones, i.e. genistein and daidzein, followed by weekly oral sensitizations with crude peanut extract plus cholera toxin and finally challenged at week 7. The anaphylactic symptoms, body temperature, peanut-specific antibodies and mast cell degranulation were assessed. Results: Soy-free diet mice showed significantly higher anaphylactic symptom scores and mast cell degranulation after challenge and higher peanut-specific antibody levels than mice fed regular chow. Introduction of a regular soy diet or an isoflavone diet to soy-free diet mice significantly suppressed the allergic reactions compared to the soy-free diet. Conclusion: Rodent diet is an important variable and needs to be taken into consideration when designing experiments involving animal models. Our results indicate that elimination of soy components from the diet enhances peanut sensitization in BALB/c mice. In addition to serving as a valuable tool to mimic human food allergy, the dietary influence on the immune response could have far-reaching consequences in research involving animal models.

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Section: Resultsmentioning

confidence: 99%

“…Isoflavones are known to induce epigenetic modifications during cancer pathogenesis [18,19]. Epigenetic mechanisms have been implicated in allergic responses [17,27].…”

Section: Discussionmentioning

confidence: 99%

Dietary Elimination of Soybean Components Enhances Allergic Immune Response to Peanuts in BALB/c Mice

Chang¹,

Song²,

Li³

et al. 2015

Int Arch Allergy Immunol

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“…IFs act as phytoestrogens and prevent tumorigenesis in rodent models via various bioactivities. IFs have been previously demonstrated to target all major epigenetic mechanisms regulating gene expression in in vitro and in vivo studies (36)(37)(38)(39)(40)(41)(42)(43). Greathouse et al (44) have recently reported that genistein-mediated phosphorylation of zeste homolog 2 was able to inhibit its activity and promote benign uterine cancers in Eker rats.…”

Section: Discussionmentioning

confidence: 99%

Mislocalization of Runt-related transcription factor 3 results in airway inflammation and airway hyper-responsiveness in a murine asthma model

Zhou

Zhu

Bian

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The Runt-related transcription factor (RUNX) gene family consists of three members, RUNX1, -2 and -3, which heterodimerize with a common protein, core-binding factor β, and contain the highly conserved Runt-homology domain. RUNX1 and -2 have essential roles in hematopoiesis and osteogenesis. Runx3 protein regulates cell lineage decisions in neurogenesis and thymopoiesis. The aim of the present study was to determine the expression features of the Runx3 protein in a murine asthma model. In vivo, Runx3 protein and mRNA were found to be almost equivalently expressed in the murine lung tissue of the control, ovalbumin (OVA) and genistein groups; however, the nuclear Runx3 protein was abated in lung tissue in OVA-immunized and challenged mice. Following treatment with genistein, which is a flavonoid previously demonstrated to decrease airway inflammation in asthma, the allergic airway inflammation and airway hyper-responsiveness were attenuated and the Runx3 protein tended to augment in the nucleus. These results were further determined in vitro. These results indicated that the mislocalization of Runx3 protein is a molecular mechanism of allergic inflammation and airway hyper-responsiveness in a murine asthma model.

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“…The actives were positive controls or compounds that showed inhibitory activity against DNMT1 through in vitro or in vivo tests. Based on the previous research, 25 compounds were chosen as actives [11][12][13][14][15][16][17]. Their structures were obtained in SMILES format from the PubChem website at pubchem.ncbi.nlm.nih.gov [33].…”

Section: Preparing the Ligand Structurementioning

confidence: 99%

“…Natural products are promising non-nucleoside DNMTi candidates because of their relatively low toxicity and high structural diversity [10,11]. The potential of several natural products has been studied; these products have included curcumin [12], epigallocatechin (EGCG) [13], genistein [14], caffeic acid [15], psammaplin A [16], mahanine [17], and laccaic acid [16]. However, the inhibitory effects of these natural compounds are relatively low [11].…”

Section: Introductionmentioning

confidence: 99%

Virtual Screening of Indonesian Herbal Database for Dna Methyltransferase Inhibitors

Bhaskarawilaputraka

Azminah

Erlina

et al. 2017

Asian J Pharm Clin Res

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Objective: DNA hypermethylation is an abnormal epigenetic process catalyzed by DNA methyltransferase 1 (DNMT1). It is also one of the factors that cause non-communicable diseases such as cancer, diabetes, and other metabolic diseases. DNA hypermethylation can be reversed by suppressing DNMT1 activity using a DNMT inhibitor. This study was conducted to seek out inhibitor candidates among natural products. Methods:The search for potential inhibitors was conducted through a virtual screening of the Indonesian Herbal Database using AutoDockVina as docking software. Twenty-five compounds known for their inhibitory activity against DNMT1 were used as actives and as a reference for generating decoys, which was done using the Directory of Useful Decoys, Enhanced. Results:The 12 compounds with binding energies below the cutoff value were cassiamin C (A1), procyanidin B2 (B2), ent-epicatechin-(4alpha->8)-ent-epicatechin (C3), epicatechin-(4beta->8)-epicatechin-3-O-gallate (D4), neorhusflavanone (E5), 3-O-galloylepicatechin-(4beta->6)-epicatechin-3-O-gallate (F6), withanolide (G7), 3-O-galloylepigallocatechin-(4beta->6)-epigallocatechin-3-O-gallate (H8), cyanidin 3-(6''-caffeylsophoroside)-5-glucoside (I9), epifriedelanol (J10), gallocatechin-(4alpha->8)-epicatechin (K11), and scutellarein 7-glucosyl-(1->4)-rhamnoside (L12). A1 had the lowest binding energy of −12.7 kcal/mol, whereas K11 had the highest of −11.5 kcal/mol. Conclusions:The virtual screening yielded five potential DNMT1 inhibitors: Procyanidin B2, ent-epicatechin-(4alpha->8)-ent-epicatechin, epicatechin-(4beta->8)-epicatechin-3-O-gallate, neorhusflavanone, and cyanidin 3-(6''-caffeylsophoroside)-5-glucoside.Keywords: Epigenetic, DNA methyltransferase inhibitor, Indonesian Herbal Database, Virtual screening, AutoDockVina. INTRODUCTIONEpigenetic modification is one of the factors that cause noncommunicable diseases. Living environment, lifestyle, exposure to toxic chemicals, and nutrition may influence an individual's epigenetic profile. Epigenetic modification can alter gene expression [1]. One type of epigenetic modification is DNA methylation. DNA methylation, catalyzed by DNA methyltransferases (DNMTs), is the addition of a methyl (CH3) group to the DNA strand, specifically to the fifth carbon atom of a cytosine ring. Methylated cytosine, called 5-methylcytosine, usually occurs to a cytosine base that lies adjacent to a guanine base, at what is called a CpG site. The reason for this name is that cytosine is bonded to guanine through a phosphate bond. These sites normally occur in clusters; an area rich in CpG sites is called a CpG island. CpG islands are usually located near a gene regulator such as a promoter. DNA methylation that affects a gene promoter may repress the transcription of said gene and ultimately its expression. This process of turning a gene on and off through methylation is part of normal eukaryotic cell function [2,3].There are several types of DNMTs. Based on their functions, they can be grouped into two categories: De novo DNMTs...

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Genistein inhibits DNA methylation and increases expression of tumor suppressor genes in human breast cancer cells

Cited by 171 publications

References 39 publications

Dietary Elimination of Soybean Components Enhances Allergic Immune Response to Peanuts in BALB/c Mice

Dietary Elimination of Soybean Components Enhances Allergic Immune Response to Peanuts in BALB/c Mice

Mislocalization of Runt-related transcription factor 3 results in airway inflammation and airway hyper-responsiveness in a murine asthma model

Virtual Screening of Indonesian Herbal Database for Dna Methyltransferase Inhibitors

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