Epigenetic Reactivation of RANK in Glioblastoma Cells by Curcumin: Involvement of STAT3 Inhibition

Wu, Bingshan; Yao, Xue-Qin; Nie, Xiaohu; Xu, Ran

doi:10.1089/dna.2013.2042

Cited by 35 publications

(19 citation statements)

References 26 publications

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“…Moreover, CUR has been demonstrated to possess direct antiangiogenic activity in vivo [ 13 – 15 ]. Further study showed that CUR exerted its antitumor activity involved in reactivation of receptor activator of NF-κB and inactivation of STAT3 in glioblastoma cells [ 16 ]. Additionally, CUR was discovered to suppress the cell growth through inhibition of histone deacetylase 4 (HADC4) and NF-κB pathways in medulloblastoma cells [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Curcumin induces G2/M cell cycle arrest and apoptosis of head and neck squamous cell carcinomain vitroandin vivothrough ATM/Chk2/p53-dependent pathway

Huang

Zhang

et al. 2017

Oncotarget

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Studies have demonstrated that curcumin (CUR) exerts its tumor suppressor function in a variety of human cancers including head and neck squamous cell carcinoma (HNSCC). However, the exact underlying molecular mechanisms remain obscure. Here, we aim to test whether CUR affects ATM/Chk2/p53 signaling pathway, leading to the induction of cell cycle arrest, inhibition of angiogenesis of HNSCC in vitro and in vivo. To this end, we conducted multiple methods such as MTT assay, Invasion assay, Flow cytometry, Western blotting, RT-PCR, and transfection to explore the functions and molecular insights of CUR in HNSCC. We observed that CUR significantly induced apoptosis and cell cycle arrest, inhibited angiogenesis in HNSCC. Mechanistically, we demonstrated that CUR markedly up-regulated ATM expression and subsequently down-regulated HIF-1α expression. Blockage of ATM production totally reversed CUR induced cell cycle arrest as well as anti-angiogenesis in HNSCC. Moreover, our results demonstrated that CUR exerts its antitumor activity through targeting ATM/Chk2/p53 signal pathway. In addition, the results of xenograft experiments in mice were highly consistent with in vitro studies. Collectively, our findings suggest that targeting ATM/Chk2/p53 signal pathway by CUR could be a promising therapeutic approach for HNSCC prevention and therapy.

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Section: Introductionmentioning

confidence: 99%

Curcumin induces G2/M cell cycle arrest and apoptosis of head and neck squamous cell carcinomain vitroandin vivothrough ATM/Chk2/p53-dependent pathway

Huang

Zhang

et al. 2017

Oncotarget

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“…Demethylation was associated with the re-activation of silenced p 16, SPARC, E-cadherin, HSP-90, and NF-κB, leading to the downregulation of DNMT-1 expression [34]. A study using U251 and U81 glioblastoma cells also showed that treatment with 30 µM curcumin for 4 days decreased the promoter hypermethylation of the receptor activator of NF-κB (RANK), resulting in RANK gene expression and activation [35]. Furthermore, in a different study, curcumin treatment in MCF-7 cells enhanced the mRNA and protein levels of Ras-association domain family protein 1A (RASSF1A) and decreased its promoter methylation.…”

Section: Introductionmentioning

confidence: 99%

“Curcumin, the King of Spices”: Epigenetic Regulatory Mechanisms in the Prevention of Cancer, Neurological, and Inflammatory Diseases

2015

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Curcumin (diferuloylmethane), a polyphenolic compound, is a component of Curcuma longa, commonly known as turmeric. It is a well-known anti-inflammatory, anti-oxidative, and anti-lipidemic agent and has recently been shown to modulate several diseases via epigenetic regulation. Many recent studies have demonstrated the role of epigenetic inactivation of pivotal genes that regulate human pathologies, such as neurocognitive disorders, inflammation, obesity, and cancers. Epigenetic changes involve changes in DNA methylation, histone modifications, or altered microRNA expression patterns which are known to be interconnected and play a key role in tumor progression and failure of conventional chemotherapy. The majority of epigenetic changes are influenced by lifestyle and diets. In this regard, dietary phytochemicals as dietary supplements have emerged as a promising source that are able to reverse these epigenetic alterations, to actively regulate gene expression and molecular targets that are known to promote tumorigenesis, and also to prevent age-related diseases through epigenetic modifications. There have been several studies which reported the role of curcumin as an epigenetic regulator in neurological disorders, inflammation, and in diabetes apart from cancers. The epigenetic regulatory roles of curcumin include (1) inhibition of DNA methyltransferases (DNMTs), which has been well defined from the recent studies on its function as a DNA hypomethylating agent; (2) regulation of histone modifications via regulation of histone acetyltransferases (HATs) and histone deacetylases (HDACs); and (3) regulation of micro RNAs (miRNA). This review summarizes the current knowledge on the effect of curcumin in the treatment and/or prevention of inflammation, neurodegenerative diseases, and cancers by regulating histone deacetylases, histone acetyltransferases, and DNA methyltransferases.

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“…Moreover, Du et al found that curcumin inhibited SHH (sonic hedgehog)/Gli1 signaling pathway, leading to inhibition of cell growth and induction of apoptosis in vitro and in vivo in glioma [ 10 ]. Further study showed that curcumin exerted its antitumor activity involved in reactivation of RANK (receptor activator of nuclear factor κB) and inactivation of STAT3 (signal transducer and activator of transcription 3) in glioblastoma cells [ 11 ]. Notably, curcumin synergistically enhanced paclitaxel-mediated cell growth inhibition in glioma cells [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Curcumin suppresses cell growth and invasion and induces apoptosis by down-regulation of Skp2 pathway in glioma cells

Wang

Cai

et al. 2015

Oncotarget

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Studies have demonstrated that curcumin exerts its tumor suppressor function in a variety of human cancers including glioma. However, the exact underlying molecular mechanisms remain obscure. Emerging evidence has revealed that Skp2 (S-phase kinase associated protein 2) plays an oncogenic role in tumorigenesis. Therefore, we aim to determine whether curcumin suppresses the Skp2 expression, leading to the inhibition of cell growth, invasion, induction of apoptosis, and cell cycle arrest. To this end, we conducted multiple methods such as MTT assay, Flow cytometry, Wound healing assay, invasion assay, RT-PCR, Western blotting, and transfection to explore the functions and molecular insights of curcumin in glioma cells. We found that curcumin significantly inhibited cell growth, suppressed cell migration and invasion, induced apoptosis and cell cycle arrest in glioma cells. Furthermore, we observed that overexpression of Skp2 promoted cell growth, migration, and invasion, whereas depletion of Skp2 suppressed cell growth, migration, and invasion and triggered apoptosis in glioma cells. Mechanistically, we defined that curcumin markedly down-regulated Skp2 expression and subsequently up-regulated p57 expression. Moreover, our results demonstrated that curcumin exerts its antitumor activity through inhibition of Skp2 pathway. Collectively, our findings suggest that targeting Skp2 by curcumin could be a promising therapeutic approach for glioma prevention and therapy.

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Epigenetic Reactivation of RANK in Glioblastoma Cells by Curcumin: Involvement of STAT3 Inhibition

Cited by 35 publications

References 26 publications

Curcumin induces G2/M cell cycle arrest and apoptosis of head and neck squamous cell carcinomain vitroandin vivothrough ATM/Chk2/p53-dependent pathway

Curcumin induces G2/M cell cycle arrest and apoptosis of head and neck squamous cell carcinomain vitroandin vivothrough ATM/Chk2/p53-dependent pathway

“Curcumin, the King of Spices”: Epigenetic Regulatory Mechanisms in the Prevention of Cancer, Neurological, and Inflammatory Diseases

Curcumin suppresses cell growth and invasion and induces apoptosis by down-regulation of Skp2 pathway in glioma cells

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