Epigallocatechin Gallate Preferentially Inhibits O<sup>6</sup>-Methylguanine DNA-Methyltransferase Expression in Glioblastoma Cells Rather than in Nontumor Glial Cells

Xie, Chaoran; You, Chaoguo; Zhang, Nu; Huang, Song; Zheng, Xiaohang

doi:10.1080/01635581.2018.1539189

Cited by 21 publications

(12 citation statements)

References 31 publications

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“…Intriguingly, there is evidence of regulation of MGMT by WNT/β-catenin signaling. EGCG not only prevented translocation of β-catenin into the nucleus but also reduced the levels of transcriptional factors TCF1 and LEF1 [46]. Overall these findings clearly suggested that EGCG repressed MGMT expression via inhibition of the β-catenin-driven pathway.…”

Section: Regulation Of Wnt/β-catenin Pathwaymentioning

confidence: 64%

EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK/STAT, Wnt/β-Catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL Mediated Signaling Pathways

Farooqi

Pinheiro

Granja

et al. 2020

Cancers

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Decades of research have enabled us to develop a better and sharper understanding of multifaceted nature of cancer. Next-generation sequencing technologies have leveraged our existing knowledge related to intra- and inter-tumor heterogeneity to the next level. Functional genomics have opened new horizons to explore deregulated signaling pathways in different cancers. Therapeutic targeting of deregulated oncogenic signaling cascades by products obtained from natural sources has shown promising results. Epigallocatechin-3-gallate (EGCG) has emerged as a distinguished chemopreventive product because of its ability to regulate a myriad of oncogenic signaling pathways. Based on its scientifically approved anticancer activity and encouraging results obtained from preclinical trials, it is also being tested in various phases of clinical trials. A series of clinical trials associated with green tea extracts and EGCG are providing clues about significant potential of EGCG to mechanistically modulate wide ranging signal transduction cascades. In this review, we comprehensively analyzed regulation of JAK/STAT, Wnt/β-catenin, TGF/SMAD, SHH/GLI, NOTCH pathways by EGCG. We also discussed most recent evidence related to the ability of EGCG to modulate non-coding RNAs in different cancers. Methylation of the genome is also a widely studied mechanism and EGCG has been shown to modulate DNA methyltransferases (DNMTs) and protein enhancer of zeste-2 (EZH2) in multiple cancers. Moreover, the use of nanoformulations to increase the bioavailability and thus efficacy of EGCG will be also addressed. Better understanding of the pleiotropic abilities of EGCG to modulate intracellular pathways along with the development of effective EGCG delivery vehicles will be helpful in getting a step closer to individualized medicines.

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Section: Regulation Of Wnt/β-catenin Pathwaymentioning

confidence: 64%

EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK/STAT, Wnt/β-Catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL Mediated Signaling Pathways

Farooqi

Pinheiro

Granja

et al. 2020

Cancers

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“…Furthermore, EGCG selectively decreased MGMT levels in glioblastoma multiforme cells by preventing translocation of b-catenin to the nucleus, thereby avoiding the removal of temozolomide-produced O6-methylguanine and helping to resensitize cells resistant to this drug. In contrast, EGCG improved MGMT expression in non-tumor glial cells by inhibiting DNMT1 and allowing demethylation of its promoter (59). Normal human leucocytes with continuous low-dose EGCG treatments show less DNA damage (single and double chain mutations, adducts, and mutations) when exposed to genotoxic agents such as bleomycin and some heterocyclic amines (60,61).…”

Section: (-)-Epigallocatechin-3-gallatementioning

confidence: 98%

Natural Compounds That Target DNA Repair Pathways and Their Therapeutic Potential to Counteract Cancer Cells

Lagunas‐Rangel

Bermúdez‐Cruz

2020

Front. Oncol.

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Resistance to current cancer treatments is an important problem that arises through various mechanisms, but one that stands out involves an overexpression of several factors associated with DNA repair. To counteract this type of resistance, different drugs have been developed to affect one or more DNA repair pathways, therefore, to test different compounds of natural origin that have been shown to induce cell death in cancer cells is paramount. Since natural compounds target components of the DNA repair pathways, they have been shown to promote cancer cells to be resensitized to current treatments. For this and other reasons, natural compounds have aroused great curiosity and several research projects are being developed around the world to establish combined treatments between them and radio or chemotherapy. In this work, we summarize the effects of different natural compounds on the DNA repair mechanisms of cancer cells and emphasize their possible application to re-sensitize these cells.

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“…Importantly, EGCG inhibits the expression of O 6 -Methylguanine DNA-Methyltransferase (MGMT) in GBM-derived cells only, which is an essential regulator of the resistance to temozolomide (TMZ) in glioblastomas. EGCG treatment in two GBM cell lines (GBM-XD and T98G) results in suppression of MGMT expression, abolishes TMZ resistance, and prevents β catenin translocation into the nucleus [107]. On the contrary, the addition of EGCG to non-tumor glial cell culture (GliaX) enhances MGMT expression by inhibiting the methylation of the MGMT promoter [107].…”

Section: Egcg Effects On Central Nervous System Cancersmentioning

confidence: 99%

“…EGCG treatment in two GBM cell lines (GBM-XD and T98G) results in suppression of MGMT expression, abolishes TMZ resistance, and prevents β catenin translocation into the nucleus [107]. On the contrary, the addition of EGCG to non-tumor glial cell culture (GliaX) enhances MGMT expression by inhibiting the methylation of the MGMT promoter [107]. Recently, it has been shown that EGCG induces telomere shortening in U251 glioblastoma, leading to senescence [108].…”

Section: Egcg Effects On Central Nervous System Cancersmentioning

confidence: 99%

Bioactive Phenolic Compounds in the Modulation of Central and Peripheral Nervous System Cancers: Facts and Misdeeds

Perrone

Sampaolo

Melone

2020

Cancers

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Efficacious therapies are not available for the cure of both gliomas and glioneuronal tumors, which represent the most numerous and heterogeneous primary cancers of the central nervous system (CNS), and for neoplasms of the peripheral nervous system (PNS), which can be divided into benign tumors, mainly represented by schwannomas and neurofibromas, and malignant tumors of the peripheral nerve sheath (MPNST). Increased cellular oxidative stress and other metabolic aspects have been reported as potential etiologies in the nervous system tumors. Thus polyphenols have been tested as effective natural compounds likely useful for the prevention and therapy of this group of neoplasms, because of their antioxidant and anti-inflammatory activity. However, polyphenols show poor intestinal absorption due to individual intestinal microbiota content, poor bioavailability, and difficulty in passing the blood–brain barrier (BBB). Recently, polymeric nanoparticle-based polyphenol delivery improved their gastrointestinal absorption, their bioavailability, and entry into defined target organs. Herein, we summarize recent findings about the primary polyphenols employed for nervous system tumor prevention and treatment. We describe the limitations of their application in clinical practice and the new strategies aimed at enhancing their bioavailability and targeted delivery.

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Epigallocatechin Gallate Preferentially Inhibits O⁶-Methylguanine DNA-Methyltransferase Expression in Glioblastoma Cells Rather than in Nontumor Glial Cells

Cited by 21 publications

References 31 publications

EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK/STAT, Wnt/β-Catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL Mediated Signaling Pathways

EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK/STAT, Wnt/β-Catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL Mediated Signaling Pathways

Natural Compounds That Target DNA Repair Pathways and Their Therapeutic Potential to Counteract Cancer Cells

Bioactive Phenolic Compounds in the Modulation of Central and Peripheral Nervous System Cancers: Facts and Misdeeds

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Epigallocatechin Gallate Preferentially Inhibits O6-Methylguanine DNA-Methyltransferase Expression in Glioblastoma Cells Rather than in Nontumor Glial Cells

Cited by 21 publications

References 31 publications

EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK/STAT, Wnt/β-Catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL Mediated Signaling Pathways

EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK/STAT, Wnt/β-Catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL Mediated Signaling Pathways

Natural Compounds That Target DNA Repair Pathways and Their Therapeutic Potential to Counteract Cancer Cells

Bioactive Phenolic Compounds in the Modulation of Central and Peripheral Nervous System Cancers: Facts and Misdeeds

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Epigallocatechin Gallate Preferentially Inhibits O⁶-Methylguanine DNA-Methyltransferase Expression in Glioblastoma Cells Rather than in Nontumor Glial Cells