2. Academic Validation
  3. Taxifolin and Lucidin as Potential E6 Protein Inhibitors: p53 Function Re-Establishment and Apoptosis Induction in Cervical Cancer Cells

Taxifolin and Lucidin as Potential E6 Protein Inhibitors: p53 Function Re-Establishment and Apoptosis Induction in Cervical Cancer Cells

  • Cancers (Basel). 2022 Jun 8;14(12):2834. doi: 10.3390/cancers14122834.
Diana Gomes 1 2 3,  Shivani Yaduvanshi 4,  Samuel Silvestre 1 5 6 7,  Ana Paula Duarte 1 5 7,  Adriana O Santos 1,  Christiane P Soares 8,  Veerendra Kumar 4,  Luís Passarinha 1 2 3 5,  Ângela Sousa 1
Affiliations

Affiliations

  • 1 CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilhã, Portugal.
  • 2 Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculdade de Ciências e Tecnologia, Universidade NOVA, 2819-516 Caparica, Portugal.
  • 3 UCIBIO-Applied Molecular Biosciences Unit, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal.
  • 4 Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University, Noida Uttar Pradesh 201303, India.
  • 5 Laboratório de Fármaco-Toxicologia-UBIMedical, Universidade da Beira Interior, 6200-284 Covilhã, Portugal.
  • 6 CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
  • 7 C4-Cloud Computing Competence Centre, UBIMedical, University of Beira Interior, Estrada Municipal 506, 6200-284 Covilhã, Portugal.
  • 8 Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Campus Ville, Araraquara, São Paulo 14800-903, Brazil.
PMID: 35740499 DOI: 10.3390/cancers14122834
Abstract

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's 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.

Keywords

E6 protein inhibitors; cervical cancer; human papillomavirus; in silico tools; lucidin; molecular docking; p53; taxifolin.

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