Dietary omega-3 polyunsaturated fatty acids suppress expression of EZH2 in breast cancer cells

Dimri, Manjari; Bommi, Prashant V.; Sahasrabuddhe, Anagh A.; Khandekar, Janardan D.; Dimri, Goberdhan P.

doi:10.1093/carcin/bgp305

Cited by 110 publications

(85 citation statements)

References 42 publications

(53 reference statements)

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“…3-Deazaneplanocin A, an s-adenosylhomocysteine hydrolase inhibitor, reduces Ezh2 and Suz12 level in MCF-7 cells, and this response is partially inhibited by proteasome inhibitors (Tan et al, 2007). In addition, omega-3 polyunsaturated fatty acids increase proteasomedependent degradation of Ezh2 in MDA-MB-231 breast cancer cells (Dimri et al, 2010). Our studies are consistent with a role for the proteasome in SFN-dependent reduction of PcG protein level in skin cancer cells.…”

Section: Discussionsupporting

confidence: 84%

“…The proteasome has been reported to be involved in PcG turnover in selected cell types (Tan et al, 2007;Dimri et al, 2010). To assess this possibility, we treated SCC-13 cells with SFN in the presence or absence of lactacystin and monitored the impact on Bmi-1, Ezh2, and H3K27me3 formation.…”

Section: Resultsmentioning

confidence: 99%

“…Recent studies highlight a role for the proteasome in regulating PcG protein level (Tan et al, 2007;Dimri et al, 2010). 3-Deazaneplanocin A, an s-adenosylhomocysteine hydrolase inhibitor, reduces Ezh2 and Suz12 level in MCF-7 cells, and this response is partially inhibited by proteasome inhibitors (Tan et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

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Sulforaphane Suppresses Polycomb Group Protein Level via a Proteasome-Dependent Mechanism in Skin Cancer Cells

Balasubramanian¹,

Chew²,

Eckert³

2011

Mol Pharmacol

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The polycomb group (PcG) genes encode a family of proteins that methylate and ubiquitinate histones to close chromatin and suppress gene expression. PcG proteins are present at elevated levels in cancer cells, and this is associated with reduced tumor suppressor protein level and enhanced cell survival. Agents that reduce PcG protein level are regarded as potentially cancer-preventative agents. Sulforaphane (SFN) is a biologically important isothiocyanate found in cruciferous vegetables that is an important candidate chemopreventive agent. However, the impact of SFN on the level and function of PcG proteins in skin cancer cells has not been assessed. We show that SFN treatment causes a concentration-dependent reduction in PcG protein (Bmi-1, Ezh2) expression in SCC-13 skin cancer cells and also reduces trimethylation of lysine 27 of histone H3. This is associated with accumulation of cells in G 2 /M phase; reduced levels of cyclin B1, cyclin A, cyclin dependent kinases 1 and 2; and increased p21Cip1 expression. Sulforaphane treatment also increases cleavage of procaspase 3, 8, and 9 and enhances PARP cleavage and apoptosis. Similar results are observed in other skin-derived cell immortalized and transformed cell lines. Forced expression of the Bmi-1 polycomb protein in SCC-13 cells reverses these effects. The SFN-dependent loss of Bmi-1 and Ezh2 is due to proteasomeassociated degradation. These results suggest that dietary isothiocyanates may suppress cancer progression by reducing PcG protein level via a proteasome-dependent mechanism, thereby inhibiting PcG-dependent pro-survival epigenetic events.

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Section: Discussionsupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

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Sulforaphane Suppresses Polycomb Group Protein Level via a Proteasome-Dependent Mechanism in Skin Cancer Cells

Balasubramanian¹,

Chew²,

Eckert³

2011

Mol Pharmacol

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“…Dimri et al 126 reported that dietary omega-3 (v-3) polyunsaturated fatty acids (PUFAs) can downregulate EZH2 expression and activity in breast cancer cells by inducing the ubiquitination and proteosomal degradation of EZH2. This PUFA-mediated inhibition resulted in the re-expression of known of the human genome project, new molecular markers have been identified.…”

Section: Ezh2 As Potential Cancer Therapeutic Targetmentioning

confidence: 99%

Multifaceted role of EZH2 in breast and prostate tumorigenesis

2013

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“…Dietary omega-3 polyunsaturated fatty acids suppress the expression of EZH2 in breast cancer cells [33]. Similarly to PcG proteins, CFTFs and long ncRNAs could also be possible diagnostic and prognostic markers, or targets for cancer treatment.…”

Section: Diagnostic and Therapeutic Implications Of Pcg Proteinsmentioning

confidence: 99%

Polycomb group proteins and their roles in carcinogenesis

Xiao

Tao

et al. 2012

Chin. Sci. Bull.

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In the cell nucleus, DNA is wound around histone proteins, which are then packed together to form chromatin. Histones can be chemically tagged by methyl and acetyl groups. Polycomb group (PcG) proteins attach methyl groups to genes, which block their activity. This is similar to the attachment of methyl groups to gene promoters by DNA methyltransferases (DNMTs). This action is directly linked with tumor initiation and metastasis via the promotion of anti-senescence and anti-apoptosis pathways, and by facilitating epithelial mesenchymal transition (EMT). Cell fate transcriptional factors (CFTFs) and long non-coding RNAs (long ncRNAs) recruit PcG proteins to the promoters of tumor suppressor genes, resulting in epigenetic gene silencing by influencing chromatin structure and DNA accessibility. Thus, PcG proteins are potential diagnostic markers and targets for new chemoprevention and therapeutic strategies. Tumorigenesis has traditionally been considered to be driven by the sequential acquisition of mutations, leading to the activation of oncogenes and to the loss of function of tumor suppressor genes. An increasingly large amount of evidence suggests that carcinogenesis also involves "epigenetic changes", which are mediated by mechanisms that do not affect the primary DNA sequence. Epigenetic changes include both genome-wide loss and regional gain of DNA methylation, and aberrant post-translation modifications of histones. Both DNA methylation and histone modification have key functions in governing gene expression by influencing chromatin structure and DNA accessibility. Abnormal chromatin structure can cause inappropriate gene expression and genomic instability, which results in cellular transformation and malignant growth. Therefore, proteins that control chromatin structure are important in carcinogenesis. Polycomb group proteins (PcG proteins), which regulate chromatin remodeling, are one such class of proteins that regulate chromatin structure. PcG proteins form multiprotein repressive complexes, called polycomb repressive complexes (PRCs). As repressors of transcription, PRCs silence specific genes by altering chromatin modification. Here we review the biological functions and the molecular mechanisms of PcG proteins in oncogenesis. We also consider the potential role of PcG proteins in the diagnosis and treatment of cancer.

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Dietary omega-3 polyunsaturated fatty acids suppress expression of EZH2 in breast cancer cells

Cited by 110 publications

References 42 publications

Sulforaphane Suppresses Polycomb Group Protein Level via a Proteasome-Dependent Mechanism in Skin Cancer Cells

Sulforaphane Suppresses Polycomb Group Protein Level via a Proteasome-Dependent Mechanism in Skin Cancer Cells

Multifaceted role of EZH2 in breast and prostate tumorigenesis

Polycomb group proteins and their roles in carcinogenesis

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