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
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 hor...
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| Veröffentlicht in: | Cancers 2020-04, Vol.12 (4), p.951 |
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| creator | Farooqi, Ammad Ahmad Pinheiro, Marina Granja, Andreia Farabegoli, Fulvia Reis, Salette Attar, Rukset Sabitaliyevich, Uteuliyev Yerzhan Xu, Baojun Ahmad, Aamir |
| description | 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. |
| doi_str_mv | 10.3390/cancers12040951 |
| format | Article |
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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.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers12040951</identifier><identifier>PMID: 32290543</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antitumor activity ; Apoptosis ; Bioavailability ; Breast cancer ; Clinical trials ; Colorectal cancer ; DNA methylation ; Drug dosages ; Epigallocatechin gallate ; Epigenetics ; Genomics ; Green tea ; Immunology ; Kinases ; Leukemia ; Lymphatic system ; Next-generation sequencing ; Non-coding RNA ; Oral cancer ; Ovarian cancer ; Phosphorylation ; Prostate cancer ; Proteins ; Regulation ; Review ; Signal transduction ; Smad protein ; Tea ; Therapeutic targets ; Tumors ; Vascular endothelial growth factor ; Wnt protein ; β-Catenin</subject><ispartof>Cancers, 2020-04, Vol.12 (4), p.951</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-aaf1a0a424626037486ca947f429f7fad1298cbe9c21e6934f4784678b03a4813</citedby><cites>FETCH-LOGICAL-c421t-aaf1a0a424626037486ca947f429f7fad1298cbe9c21e6934f4784678b03a4813</cites><orcidid>0000-0002-6931-1355 ; 0000-0003-0739-3735 ; 0000-0003-2899-5014 ; 0000-0003-1784-5723</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226503/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226503/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32290543$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Farooqi, Ammad Ahmad</creatorcontrib><creatorcontrib>Pinheiro, Marina</creatorcontrib><creatorcontrib>Granja, Andreia</creatorcontrib><creatorcontrib>Farabegoli, Fulvia</creatorcontrib><creatorcontrib>Reis, Salette</creatorcontrib><creatorcontrib>Attar, Rukset</creatorcontrib><creatorcontrib>Sabitaliyevich, Uteuliyev Yerzhan</creatorcontrib><creatorcontrib>Xu, Baojun</creatorcontrib><creatorcontrib>Ahmad, Aamir</creatorcontrib><title>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</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Decades of research have enabled us to develop a better and sharper understanding of multifaceted nature of cancer. 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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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32290543</pmid><doi>10.3390/cancers12040951</doi><orcidid>https://orcid.org/0000-0002-6931-1355</orcidid><orcidid>https://orcid.org/0000-0003-0739-3735</orcidid><orcidid>https://orcid.org/0000-0003-2899-5014</orcidid><orcidid>https://orcid.org/0000-0003-1784-5723</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancers, 2020-04, Vol.12 (4), p.951 |
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| language | eng |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | Antitumor activity Apoptosis Bioavailability Breast cancer Clinical trials Colorectal cancer DNA methylation Drug dosages Epigallocatechin gallate Epigenetics Genomics Green tea Immunology Kinases Leukemia Lymphatic system Next-generation sequencing Non-coding RNA Oral cancer Ovarian cancer Phosphorylation Prostate cancer Proteins Regulation Review Signal transduction Smad protein Tea Therapeutic targets Tumors Vascular endothelial growth factor Wnt protein β-Catenin |
| title | 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 |
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