Curcumin Reactivates Silenced Tumor Suppressor Gene RARβ by Reducing DNA Methylation

Jiang, Apei; Wang, Xuemin; Xu, Shan; Li, Yuan; Wang, Pengqi; Jiang, Pan; Feng, Qing

doi:10.1002/ptr.5373

Cited by 81 publications

(41 citation statements)

References 29 publications

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“…Results of the present study demonstrate that low concentrations of 5 and 10 µM curcumin increase the expression level of CRABPII, while concomitantly induces expression of its cognate receptor, RARβ and RARγ. Similarly, a recent study demonstrated that curcumin upregulated the expression of RARβ in several cancer cells, including TNBC MDA-MB-231 cells and activated RARβ via epigenetic regulation (22). Though the RAR subtypes have different functions and regulate distinct RARE targeted genes, RAR signaling plays a critical role in cancer progression.…”

Section: Discussionmentioning

confidence: 96%

Activation of the CRABPII/RAR pathway by curcumin induces retinoic acid mediated apoptosis in retinoic acid resistant breast cancer cells

et al. 2017

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Due to the anti-proliferative and anti-apoptotic effects of retinoic acid (RA), this hormone has emerged as a target for several diseases, including cancer. However, development of retinoid resistance is a critical issue and efforts to understand the retinoid signaling pathway may identify useful biomarkers for future clinical trials. Apoptotic responses of RA are exhibited through the cellular RA-binding protein II (CRABPII)/retinoic acid receptor (RAR) signaling cascade. Delivery of RA to RAR by CRABPII enhances the transcriptional activity of genes involved in cell death and cell cycle arrest. The purpose of this study was to investigate the role of curcumin in sensitizing RA-resistant triple-negative breast cancer (TNBC) cells to RA-mediated apoptosis. We provide evidence that curcumin upregulates the expression of CRABPII, RARβ and RARγ in two different TNBC cell lines. Co-treatment of the cells with curcumin and RA results in increased apoptosis as demonstrated by elevated cleavage of poly(ADP-ribose) polymerase and cleaved caspase-9. Additionally, silencing CRABPII reverses curcumin sensitization of TNBC cells to the apoptotic inducing effects of RA. These findings provide mechanistic insights into sensitizing TNBC cells to RA-mediated cell death by curcumin-induced upregulation of the CRABPII/RAR pathway.

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Section: Discussionmentioning

confidence: 96%

Activation of the CRABPII/RAR pathway by curcumin induces retinoic acid mediated apoptosis in retinoic acid resistant breast cancer cells

et al. 2017

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“…Four lung tumor lines treated with 5-aza-2’-deoxycytidine, restored RARβ expression and resulted in decreased tumorigenicity [15]. In addition, curcumin can increase RARβ expression at the mRNA and protein levels in lung cancer A549 and H460 cells, indicating that curcumin is able to inhibit RARβ promoter methylation [35]. The clinical trials have shown the therapeutic potential by reactivation of tumor suppressor expression and may shed light on cancer treatment through gene-targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

Association between Retinoicacid receptor-βhypermethylation and NSCLC risk: a meta-analysis and literature review

Li¹,

Lyu

et al. 2016

Oncotarget

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Emerging evidence indicates that Retinoic acid receptor-β (RARβ) is a tumor suppressor in many types of tumor. However, whether or not RARβ is a risk factor and is correlated to clinicopathological characteristics of non-small cell lung cancer (NSCLC) remains unclear. In this report, we performed a meta-analysis to determine the effects of RARβ hypermethylation on the incidence of NSCLC and clinicopathological characteristics in human NSCLC patients. Final valuation and analysis of 1780 cancer patients from 16 eligible studies was performed. RARβ hypermethylation was found to be significantly higher in NSCLC than in normal lung tissue, the pooled OR from 7 studies including 646 NSCLC and 580 normal lung tissues, OR = 6.05, 95% CI = 3.56-10.25, p<0.00001. RARβ hypermethylation was significantly higher in adenocarcinoma (AC) compared to squamous cell carcinoma (SCC), pooled OR is 0.68 (95% CI = 0.52-0.89, p = 0.005). RARβ hypermethylation was also found to occur significantly higher in smoker (n = 232) than non-smoker (n = 213) (OR = 2.46, 95% CI = 1.54-3.93, p = 0.0002). Our results indicate that RARβ hypermethylation correlates well with an increased risk in NSCLC patients. RARβ geneinactivation caused by RARβ methylation contributes the NSCLC tumorigenesis and may serve as a potential risk factor, diagnostic marker and drug target of NSCLC.

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“…These studies underline the importance of curcumin-mediated modulation of miRNAs as an important mechanism for its biological effects. Curcumin has been reported to reduce DNMT3B activation leading to hypomethylation of RARβ resulting in upregulation of its expression [105]. Dendrasomal curcumin has been shown to induce DNA hypomethylation in part via up-regulation of epi-miRs, leading to the re-expression of silenced tumor suppressor genes including MEG3 , and suppress oncogenes including HOTAIR, targeting histone modifying complexes in hepatocellular carcinoma HCC cells [106].…”

Section: 0 Epigenetic Mechanisms Regulated By Dietary Phytochemicalsmentioning

confidence: 99%

Dietary phytochemicals as epigenetic modifiers in cancer: Promise and challenges

Shankar

Kanwal

Candamo

et al. 2016

Seminars in Cancer Biology

124

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The influence of diet and environment on human health has been known since ages. Plant-derived natural bioactive compounds (phytochemicals) have acquired an important role in human diet as potent antioxidants and cancer chemopreventive agents. In past few decades, the role of epigenetic alterations such as DNA methylation, histone modifications and non-coding RNAs in the regulation of mammalian genome have been comprehensively addressed. Although the effects of dietary phytochemicals on gene expression and signaling pathways have been widely studied in cancer, the impact of these dietary compounds on mammalian epigenome is rapidly emerging. The present review outlines the role of different epigenetic mechanisms in the regulation and maintenance of mammalian genome and focuses on the role of dietary phytochemicals as epigenetic modifiers in cancer. Above all, the review focuses on summarizing the progress made thus far in cancer chemoprevention with dietary phytochemicals, the heightened interest and challenges in the future.

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Curcumin Reactivates Silenced Tumor Suppressor Gene RARβ by Reducing DNA Methylation

Cited by 81 publications

References 29 publications

Activation of the CRABPII/RAR pathway by curcumin induces retinoic acid mediated apoptosis in retinoic acid resistant breast cancer cells

Activation of the CRABPII/RAR pathway by curcumin induces retinoic acid mediated apoptosis in retinoic acid resistant breast cancer cells

Association between Retinoicacid receptor-βhypermethylation and NSCLC risk: a meta-analysis and literature review

Dietary phytochemicals as epigenetic modifiers in cancer: Promise and challenges

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