Curcumin Down-Regulates DNA Methyltransferase 1 and Plays an Anti-Leukemic Role in Acute Myeloid Leukemia

Yu, Jianhua; Peng, Yong; Wu, Lai-Chu; Xie, Zhiliang; Deng, Youcai; Hughes, Tiffany; He, Shasha; Mo, Xiao kui; Chiu, Ming; Wang, Qi En; He, Xiaoming; Liu, Shujun; Grever, Michael R.; Chan, Kenneth K.; Liu, Zhongfa

doi:10.1371/journal.pone.0055934

Cited by 130 publications

(115 citation statements)

References 34 publications

(37 reference statements)

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“…There are Sp1 binding sites on DNMT1 (39) and Yu et al (40) observed that curcumin inhibits DNMT1 expression, possibly by inhibiting Sp1 activity. Similar results were observed by Du et al (41).…”

Section: Discussionmentioning

confidence: 99%

Casticin inhibits the activity of transcription factor Sp1 and the methylation of RECK in MGC803 gastric cancer cells

Yang

Huang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The present study investigated the effect of casticin on reversion-inducing-cysteine-rich protein with kazal motifs (RECK) gene expression and intracellular methylation levels in MGC803 gastric cancer cells. Cells were treated with 1, 10 and 30 µmol/l casticin. Western blotting and reverse transcription-quantitative polymerase chain reaction assays were performed to determine the protein expression and mRNA levels of RECK and DNA methyltransferase 1 (DNMT1), respectively. High-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry was used to detect RECK methylation. In addition, MGC803 cell proliferation was measured by an MTT assay and the DNA-binding activity of transcription factor Sp1 was determined using an enzyme-linked immunosorbent assay. The results demonstrated that treatment with 1, 10 and 30 µmol/l casticin significantly increased RECK protein expression and mRNA levels. In addition, casticin (30 µmol/l) decreased RECK promoter methylation levels by 31%, global DNA methylation levels by 39% and nuclear methylation activity by 71.6%. Furthermore, casticin downregulated the mRNA levels and protein expression of DNMT1. The MTT assay demonstrated that MGC803 cell proliferation was inhibited by casticin treatment and DNA binding assays indicated that casticin reduced the DNA-binding activity of Sp1. The present study therefore indicated that casticin inhibits the proliferation of gastric cancer MGC803 cells by upregulating RECK gene expression and reducing intracellular methylation levels.

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Section: Discussionmentioning

confidence: 99%

Casticin inhibits the activity of transcription factor Sp1 and the methylation of RECK in MGC803 gastric cancer cells

Yang

Huang

et al. 2016

Experimental and Therapeutic Medicine

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“…Several studies have also reported that CUR could inhibit the activity or expression of DNMTs (40,42). Further, the effect of CUR and its analogues EF31 and UBS109 on inhibiting HSP-90 and NF-κB, the positive regulators of DNMT-1 transcription, has been suggested as a possible mechanism responsible for downregulation of DNMT-1 (25).…”

Section: Inhibition Of Akt/nf-κb Signaling By Cur Is Associated With mentioning

confidence: 99%

Curcumin Inhibits the AKT/NF-κB Signaling via CpG Demethylation of the Promoter and Restoration of NEP in the N2a Cell Line

Deng

Wang

et al. 2014

AAPS J

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Abstract. Curcumin (CUR), a non-toxic polyphenol from Curcuma longa, has been investigated as a potential therapy with anti-inflammatory and anti-oxidative effects for Alzheimer's disease (AD), which depicts features of chronic inflammatory environment resulting in cellular death. However, it remains largely unknown whether the anti-inflammatory effect of CUR in AD is associated with its property of CpG demethylation, which is another function of CUR with the most research interest during recent years. Neprilysin (NEP, EP24.11), a zinc-dependent metallopeptidase expressed relatively low in the brain, is emerging as a potent inhibitor of AKT/Protein Kinase B. In addition, hypermethylated promoter of NEP has been reported to be associated with decreases in NEP expression. In the present study, using bisulfite-sequencing PCR (BSP) assay, we showed that the CpG sites in NEP gene were hypermethylated both in wild-type mouse neuroblastoma N2a cells (N2a/wt) and N2a cells stably expressing human Swedish mutant amyloid precursor protein (APP) (N2a/APPswe) associated with familial early onset AD. CUR treatment induced restoration of NEP gene via CpG demethylation. This CUR-mediated upregulation of NEP expression was also concomitant with the inhibition of AKT, subsequent suppression of nuclear transcription factor-κB (NF-κB) and its downstream pro-inflammatory targets including COX-2, iNOS in N2a/APPswe cells. This study represents the first evidence on a link between CpG demethylation effect on NEP and anti-inflammation ability of CUR that may provide a novel mechanistic insight into the anti-inflammatory actions of CUR as well as new basis for using CUR as a therapeutic intervention for AD.

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“…Curcumin acts at the gene level and triggers many metabolic pathways [11,12] . It inhibits genes contributing to multidrug resistance and can modulate epigenetic phenomena by inhibiting the methyltransferase 1 in AML cells [13,14] .…”

Section: Cell Staining and Analysis For γH2ax And The Cell Cyclementioning

confidence: 99%

Epicatechin acts synergistically with curcumin-induced cytogenotoxic effect in acute promyelocytic leukemia HL-60 cell line

Papież¹,

Krzyściak²

2017

JUMD

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How to cite this article: Papież MA, Krzyściak W. Epicatechin acts synergistically with curcumin-induced cytogenotoxic effect in acute promyelocytic leukemia HL-60 cell line. J Unexplored Med Data 2017;2:52-9. Aim:The low bioavailability of curcumin, a polyphenol, limits its use as an antitumor agent. Identifying mechanisms to improve the bioavailability and effectiveness of curcumin can modify utilization of other plant-derived phenolic compounds. This study was conducted with an aim to determine the influence of some flavonoids on the effects of curcumin in an HL-60 cell line. Methods: Cells were incubated in the presence of different concentrations of curcumin and several flavonoids for 20 h. Cytotoxicity was evaluated using propidium iodide staining. The evaluation of γH2AX expression using a specific antibody, together with study of the cell cycle, was analyzed using flow cytometry. Results: A synergistic effect was obtained only using a combination of curcumin and lower concentrations of epicatechin. The low concentration of quercetin exerted an additive effect only in combination with curcumin. Moreover, incubation with curcumin and epicatechin resulted in a significant increase in the γH2AX level. Conclusion: Combination treatment with epicatechin and curcumin can potentially be considered for improving the effectiveness and bioavailability of curcumin in cell lines of myeloid leukemia. Key words:Polyphenols, cytotoxic effect, γ-H2AX, flow cytometry, HL-60 cell line ABSTRACTArticle history:

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Curcumin Down-Regulates DNA Methyltransferase 1 and Plays an Anti-Leukemic Role in Acute Myeloid Leukemia

Cited by 130 publications

References 34 publications

Casticin inhibits the activity of transcription factor Sp1 and the methylation of RECK in MGC803 gastric cancer cells

Casticin inhibits the activity of transcription factor Sp1 and the methylation of RECK in MGC803 gastric cancer cells

Curcumin Inhibits the AKT/NF-κB Signaling via CpG Demethylation of the Promoter and Restoration of NEP in the N2a Cell Line

Epicatechin acts synergistically with curcumin-induced cytogenotoxic effect in acute promyelocytic leukemia HL-60 cell line

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