Development of breast cancer spheroids to evaluate cytotoxic response to an anticancer peptide

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  • dc.contributor.author Cavaco, Marco
  • dc.contributor.author Fraga, Patrícia
  • dc.contributor.author Valle, Javier
  • dc.contributor.author Andreu Martínez, David
  • dc.contributor.author Castanho, Miguel A.R.B.
  • dc.contributor.author Neves, Vera
  • dc.date.accessioned 2021-12-16T06:56:22Z
  • dc.date.available 2021-12-16T06:56:22Z
  • dc.date.issued 2021
  • dc.description.abstract Breast cancer (BC) is the most commonly diagnosed cancer in women and one of the most common causes of cancer-related deaths. Despite intense research efforts, BC treatment still remains challenging. Improved drug development strategies are needed for impactful benefit to patients. Current preclinical studies rely mostly on cell-based screenings, using two-dimensional (2D) cell monolayers that do not mimic in vivo tumors properly. Herein, we explored the development and characterization of three-dimensional (3D) models, named spheroids, of the most aggressive BC subtypes (triple-negative breast cancer-TNBC; and human-epidermal growth receptor-2-HER2+), using the liquid overlay technique with several selected cell lines. In these cell line-derived spheroids, we studied cell density, proliferation, ultrastructure, apoptosis, reactive oxygen species (ROS) production, and cell permeabilization (live/dead). The results showed a formation of compact and homogeneous spheroids on day 7 after seeding 2000 cells/well for MDA-MB-231 and 5000 cells/well for BT-20 and BT-474. Next, we compared the efficacy of a model anticancer peptide (ACP) in cell monolayers and spheroids. Overall, the results demonstrated spheroids to be less sensitive to treatment than cell monolayers, revealing the need for more robust models in drug development.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Cavaco M, Fraga P, Valle J, Andreu D, Castanho MARB, Neves V. Development of breast cancer spheroids to evaluate cytotoxic response to an anticancer peptide. Pharmaceutics. 2021;13(11):1863. DOI: 10.3390/pharmaceutics13111863
  • dc.identifier.doi http://dx.doi.org/10.3390/pharmaceutics13111863
  • dc.identifier.issn 1999-4923
  • dc.identifier.uri http://hdl.handle.net/10230/49234
  • dc.language.iso eng
  • dc.publisher MDPI
  • dc.relation.ispartof Pharmaceutics. 2021;13(11):1863
  • dc.rights © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword 3D cell culture
  • dc.subject.keyword Anticancer peptides
  • dc.subject.keyword Breast cancer
  • dc.subject.keyword Cell monolayers
  • dc.subject.keyword Preclinical studies
  • dc.subject.keyword Spheroids
  • dc.title Development of breast cancer spheroids to evaluate cytotoxic response to an anticancer peptide
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion