{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T18:37:21Z","timestamp":1775068641327,"version":"3.50.1"},"reference-count":122,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,12]],"date-time":"2020-04-12T00:00:00Z","timestamp":1586649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011929","name":"Programa Operacional Tem\u00e1tico Factores de Competitividade","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-30624"],"award-info":[{"award-number":["POCI-01-0145-FEDER-30624"]}],"id":[{"id":"10.13039\/501100011929","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/BTM-MAT\/30624\/2017"],"award-info":[{"award-number":["PTDC\/BTM-MAT\/30624\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\/\u03b2-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.<\/jats:p>","DOI":"10.3390\/cancers12040951","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T10:41:52Z","timestamp":1586774512000},"page":"951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK\/STAT, Wnt\/\u03b2-Catenin, TGF\/SMAD, NOTCH, SHH\/GLI, and TRAIL Mediated Signaling Pathways"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2899-5014","authenticated-orcid":false,"given":"Ammad Ahmad","family":"Farooqi","sequence":"first","affiliation":[{"name":"Institute of Biomedical and Genetic Engineering (IBGE), Islamabad 54000, Pakistan"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6931-1355","authenticated-orcid":false,"given":"Marina","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Andreia","family":"Granja","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Fulvia","family":"Farabegoli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, 40126 Bologna, Italy"}]},{"given":"Salette","family":"Reis","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Rukset","family":"Attar","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Yeditepe University, Ata\u015fehir\/\u0130stanbul 34755, Turkey"}]},{"given":"Uteuliyev Yerzhan","family":"Sabitaliyevich","sequence":"additional","affiliation":[{"name":"Department of Health Policy and Health Care Development, Kazakh Medical University of Continuing Education, Almaty 050004, Kazakhstan"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0739-3735","authenticated-orcid":false,"given":"Baojun","family":"Xu","sequence":"additional","affiliation":[{"name":"Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai 519087, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1784-5723","authenticated-orcid":false,"given":"Aamir","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205, USA"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nrc2641","article-title":"Cancer prevention by tea: Animal studies, molecular mechanisms and human relevance","volume":"9","author":"Yang","year":"2009","journal-title":"Nat. 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