Development of Breast Cancer Spheroids to Evaluate Cytotoxic Response to an Anticancer Peptide
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 preclinic...
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oai:doaj.org-article:f01c0e8ba06d4b4390251fcc52ee3d032021-11-25T18:41:15ZDevelopment of Breast Cancer Spheroids to Evaluate Cytotoxic Response to an Anticancer Peptide10.3390/pharmaceutics131118631999-4923https://doaj.org/article/f01c0e8ba06d4b4390251fcc52ee3d032021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1863https://doaj.org/toc/1999-4923Breast 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.Marco CavacoPatrícia FragaJavier ValleDavid AndreuMiguel A. R. B. CastanhoVera NevesMDPI AGarticle3D cell cultureanticancer peptidesbreast cancercell monolayerspreclinical studiesspheroidsPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1863, p 1863 (2021) |
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3D cell culture anticancer peptides breast cancer cell monolayers preclinical studies spheroids Pharmacy and materia medica RS1-441 |
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3D cell culture anticancer peptides breast cancer cell monolayers preclinical studies spheroids Pharmacy and materia medica RS1-441 Marco Cavaco Patrícia Fraga Javier Valle David Andreu Miguel A. R. B. Castanho Vera Neves Development of Breast Cancer Spheroids to Evaluate Cytotoxic Response to an Anticancer Peptide |
description |
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. |
format |
article |
author |
Marco Cavaco Patrícia Fraga Javier Valle David Andreu Miguel A. R. B. Castanho Vera Neves |
author_facet |
Marco Cavaco Patrícia Fraga Javier Valle David Andreu Miguel A. R. B. Castanho Vera Neves |
author_sort |
Marco Cavaco |
title |
Development of Breast Cancer Spheroids to Evaluate Cytotoxic Response to an Anticancer Peptide |
title_short |
Development of Breast Cancer Spheroids to Evaluate Cytotoxic Response to an Anticancer Peptide |
title_full |
Development of Breast Cancer Spheroids to Evaluate Cytotoxic Response to an Anticancer Peptide |
title_fullStr |
Development of Breast Cancer Spheroids to Evaluate Cytotoxic Response to an Anticancer Peptide |
title_full_unstemmed |
Development of Breast Cancer Spheroids to Evaluate Cytotoxic Response to an Anticancer Peptide |
title_sort |
development of breast cancer spheroids to evaluate cytotoxic response to an anticancer peptide |
publisher |
MDPI AG |
publishDate |
2021 |
url |
https://doaj.org/article/f01c0e8ba06d4b4390251fcc52ee3d03 |
work_keys_str_mv |
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