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FCT","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}]},{"name":"the doctoral fellowship from FCT","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"the doctoral fellowship from FCT","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"the doctoral fellowship from FCT","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"the doctoral fellowship from FCT","award":["2020.06792.BD"],"award-info":[{"award-number":["2020.06792.BD"]}]},{"name":"the doctoral fellowship from FCT","award":["BT\/RLF\/Re-entry\/64\/2017"],"award-info":[{"award-number":["BT\/RLF\/Re-entry\/64\/2017"]}]},{"name":"the Ramalingaswami Fellowship, Department of Biotechnology, Govt. of India","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}]},{"name":"the Ramalingaswami Fellowship, Department of Biotechnology, Govt. of India","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"the Ramalingaswami Fellowship, Department of Biotechnology, Govt. of India","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"the Ramalingaswami Fellowship, Department of Biotechnology, Govt. of India","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"the Ramalingaswami Fellowship, Department of Biotechnology, Govt. of India","award":["2020.06792.BD"],"award-info":[{"award-number":["2020.06792.BD"]}]},{"name":"the Ramalingaswami Fellowship, Department of Biotechnology, Govt. of India","award":["BT\/RLF\/Re-entry\/64\/2017"],"award-info":[{"award-number":["BT\/RLF\/Re-entry\/64\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cervical cancer is the fourth leading cause of death in women worldwide, with 99% of cases associated with a human papillomavirus (HPV) infection. Given that HPV prophylactic vaccines do not exert a therapeutic effect in individuals previously infected, have low coverage of all HPV types, and have poor accessibility in developing countries, it is unlikely that HPV-associated cancers will be eradicated in the coming years. Therefore, there is an emerging need for the development of anti-HPV drugs. Considering HPV E6\u2019s oncogenic role, this protein has been proposed as a relevant target for cancer treatment. In the present work, we employed in silico tools to discover potential E6 inhibitors, as well as biochemical and cellular assays to understand the action of selected compounds in HPV-positive cells (Caski and HeLa) vs. HPV-negative (C33A) and non-carcinogenic (NHEK) cell lines. In fact, by molecular docking and molecular dynamics simulations, we found three phenolic compounds able to dock in the E6AP binding pocket of the E6 protein. In particular, lucidin and taxifolin were able to inhibit E6-mediated p53 degradation, selectively reduce the viability, and induce apoptosis in HPV-positive cells. Altogether, our data can be relevant for discovering promising leads for the development of specific anti-HPV drugs.<\/jats:p>","DOI":"10.3390\/cancers14122834","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T10:49:14Z","timestamp":1654771754000},"page":"2834","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Taxifolin and Lucidin as Potential E6 Protein Inhibitors: p53 Function Re-Establishment and Apoptosis Induction in Cervical Cancer Cells"],"prefix":"10.3390","volume":"14","author":[{"given":"Diana","family":"Gomes","sequence":"first","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA, 2819-516 Caparica, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"}]},{"given":"Shivani","family":"Yaduvanshi","sequence":"additional","affiliation":[{"name":"Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University, Noida Uttar Pradesh 201303, India"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4297-5108","authenticated-orcid":false,"given":"Samuel","family":"Silvestre","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Laborat\u00f3rio de F\u00e1rmaco-Toxicologia-UBIMedical, Universidade da Beira Interior, 6200-284 Covilh\u00e3, Portugal"},{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"C4\u2014Cloud Computing Competence Centre, UBIMedical, University of Beira Interior, Estrada Municipal 506, 6200-284 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3333-5977","authenticated-orcid":false,"given":"Ana Paula","family":"Duarte","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Laborat\u00f3rio de F\u00e1rmaco-Toxicologia-UBIMedical, Universidade da Beira Interior, 6200-284 Covilh\u00e3, Portugal"},{"name":"C4\u2014Cloud Computing Competence Centre, UBIMedical, University of Beira Interior, Estrada Municipal 506, 6200-284 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1224-9191","authenticated-orcid":false,"given":"Adriana O.","family":"Santos","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}]},{"given":"Christiane P.","family":"Soares","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Campus Ville, Araraquara, S\u00e3o Paulo 14800-903, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9241-1303","authenticated-orcid":false,"given":"Veerendra","family":"Kumar","sequence":"additional","affiliation":[{"name":"Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University, Noida Uttar Pradesh 201303, India"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6910-7576","authenticated-orcid":false,"given":"Lu\u00eds","family":"Passarinha","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA, 2819-516 Caparica, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"},{"name":"Laborat\u00f3rio de F\u00e1rmaco-Toxicologia-UBIMedical, Universidade da Beira Interior, 6200-284 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9155-7581","authenticated-orcid":false,"given":"\u00c2ngela","family":"Sousa","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3116","DOI":"10.3389\/fmicb.2019.03116","article-title":"Human Papillomavirus E6 and E7: The Cervical Cancer Hallmarks and Targets for Therapy","volume":"10","author":"Pal","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.mrrev.2016.06.005","article-title":"Clinical relevance and implications of HPV-induced neoplasia in different anatomical locations","volume":"772","author":"Prigge","year":"2017","journal-title":"Mutat. Res. 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