Synergistic epigenetic reactivation of estrogen receptor-α (ERα) by combined green tea polyphenol and histone deacetylase inhibitor in ERα-negative breast cancer cells

Li, Yuanyuan; Yuan, Yih-Ying; Meeran, Syed Musthapa; Tollefsbol, Trygve O.

doi:10.1186/1476-4598-9-274

Cited by 173 publications

(181 citation statements)

References 29 publications

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“…Interestingly, we found that CuB inhibited the expression of both DNMTs and HDACs in these cells. Previous studies have shown that treatment with either DNMTs inhibitor alone or in combination with HDACs inhibitor altered the expressions of TSGs and TPGs in many cancers (3,21,28,30). In general, promoter regions of the TSGs are hypermethylated causing their silencing in cancer and treatment with DNMTs inhibitor has been shown to reactivate their expression by altering their methylation status (28).…”

Section: Discussionmentioning

confidence: 99%

Cucurbitacin B Alters the Expression of Tumor-Related Genes by Epigenetic Modifications in NSCLC and Inhibits NNK-Induced Lung Tumorigenesis

Shukla

Khan

Kumar

et al. 2015

Cancer Prevention Research

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Non-small cell lung cancer (NSCLC) represents almost 85% of total diagnosed lung cancer. Studies have shown that combination of DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors is effective against various cancers, including lung cancer. However, optimizing the synergistic dose regime is very difficult and involves adverse side effects. Therefore, in this study, we have shown that cucurbitacin B (CuB), a single bioactive triterpenoid compound, inhibits both DNMTs and HDACs starting at a very low dose of 60 nmol/L in NSCLC H1299 cells. The CuB-mediated inhibition of DNMTs and HDACs in H1299 cells leads to the reactivation of key tumor suppressor genes (TSG) such as CDKN1A and CDKN2A, as well as downregulation of oncogenes c-MYC and K-RAS and key tumor promoter gene (TPG), human telomerase reverse transcriptase (hTERT). The upregulation of TSGs and downregulation of TPG were consistently correlated with the alterations in their promoter methylation and histone modifications. This altered expression of TPG and TSGs is, at least in part, responsible for the inhibition of cellular proliferation and induction of cellular apoptosis in NSCLC. Furthermore, CuB treatment significantly inhibited the tumor incidence and multiplicity in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice, which was associated with the induction of apoptosis and inhibition of hyperproliferation in the lung tissues. Together, our study provides new insight into the CuB-mediated epigenetic alterations and its chemotherapeutic effects on lung cancer. Cancer Prev Res; 8(6); 552-62. Ó2015 AACR.

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Section: Discussionmentioning

confidence: 99%

Cucurbitacin B Alters the Expression of Tumor-Related Genes by Epigenetic Modifications in NSCLC and Inhibits NNK-Induced Lung Tumorigenesis

Shukla

Khan

Kumar

et al. 2015

Cancer Prevention Research

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“…EGCG synergistically increased anticancer effects of the drug and sensitized ER-negative breast cancer cells to TSA. 20 Regarding the effect of EGCG in prostate cancer, EGCG could enhance the effect of androgen deprivation-based treatments improving the hormonotherapy outcome. EGCG has been shown to antagonize androgen action and decrease androgen receptor (AR) expression in hormone responsive prostate cancer cells.…”

Section: Receptor Interaction In Hormone-related Cancersmentioning

confidence: 99%

Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy

et al. 2013

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s u m m a r yBackground & aims: Green tea catechins, especially epigallocatechin-3-gallate (EGCG), have been associated with cancer prevention and treatment. This has resulted in an increased number of studies evaluating the effects derived from the use of this compound in combination with chemo/radiotherapy. This review aims at compiling latest literature on this subject. Methods: Keywords including EGCG, cancer, chemotherapy, radiotherapy and side effects, were searched using PubMed and ScienceDirect databases to identify, analyze, and summarize the research literature on this topic. Most of the studies on this subject up to date are preclinical. Relevance of the findings, impact factor, and date of publication were critical parameters for the studies to be included in the review. Results: Additive and synergistic effects of EGCG when combined with conventional cancer therapies have been proposed, and its anti-inflammatory and antioxidant activities have been related to amelioration of cancer therapy side effects. However, antagonistic interactions with certain anticancer drugs might limit its clinical use. Conclusions: The use of EGCG could enhance the effect of conventional cancer therapies through additive or synergistic effects as well as through amelioration of deleterious side effects. Further research, especially at the clinical level, is needed to ascertain the potential role of EGCG as adjuvant in cancer therapy.

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“…Human health largely depends on a healthy enteric system which may be maintained by regular intake of fruits and vegetables [110][111][112][113][114][115]. Dietary nutrients, probiotics and metabolites derived from enteric symbionts are now established for their utility in improving, gut physiology, immunity, and ultimately a better health.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Nutraceuticals as Chemopreventive and Therapeutic agents in Gut Associated Pathogenesis

Ahmad¹,

Nasiruddin²,

Khan³

et al. 2016

Biochem Anal Biochem

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Nutraceuticals have gained great insights in recent years due to their therapeutic implications. Secondary metabolites like glutamate, flavonoids, polyphenols and terpenoids are widespread in nature and are part of human diet. Polysaccharides of prebiotic nature are used both as therapeutic and prophylactic agents. These nutraceuticals in recent times have been reported to posses great potential to reduce antigenic and oxidative pressure in the human gut. Antioxidant rich diet is a potential therapeutic agent against reactive oxygen species induced pathogenesis. Epegenetic compounds present in antioxidant and prebiotics rich nutraceuticals mitigate and remove the causative factors associated with pathogenesis. Flavonoids and polyphenols exhibit antioxidant properties and have been recognized as potential gastroprotective agents and epigenetic modulators as well. Triterpenoids such as cucurbitacin is reported to posses anticancer activities. Glutamate is an enteric neurotransmitter that is used in improving neonatal gut function. This review comprehensively summarizes the current knowledge of gut modulating nutraceuticals which ultimately can play its role from prophylaxis of gut to its therapeutics by employing various macro and micro molecular pathways.

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Synergistic epigenetic reactivation of estrogen receptor-α (ERα) by combined green tea polyphenol and histone deacetylase inhibitor in ERα-negative breast cancer cells

Cited by 173 publications

References 29 publications

Cucurbitacin B Alters the Expression of Tumor-Related Genes by Epigenetic Modifications in NSCLC and Inhibits NNK-Induced Lung Tumorigenesis

Cucurbitacin B Alters the Expression of Tumor-Related Genes by Epigenetic Modifications in NSCLC and Inhibits NNK-Induced Lung Tumorigenesis

Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy

Nutraceuticals as Chemopreventive and Therapeutic agents in Gut Associated Pathogenesis

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