Crotoxin Modulates Events Involved in Epithelial–Mesenchymal Transition in 3D Spheroid Model

Epithelial–mesenchymal transition (EMT) occurs in the early stages of embryonic development and plays a significant role in the migration and the differentiation of cells into various types of tissues of an organism. However, tumor cells, with altered form and function, use the EMT process to migrat...

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Autores principales: Ellen Emi Kato, Sandra Coccuzzo Sampaio
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Lenguaje:EN
Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/f6b26b6954c3409d81dd60f24a5c69bd
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spelling oai:doaj.org-article:f6b26b6954c3409d81dd60f24a5c69bd2021-11-25T19:09:12ZCrotoxin Modulates Events Involved in Epithelial–Mesenchymal Transition in 3D Spheroid Model10.3390/toxins131108302072-6651https://doaj.org/article/f6b26b6954c3409d81dd60f24a5c69bd2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6651/13/11/830https://doaj.org/toc/2072-6651Epithelial–mesenchymal transition (EMT) occurs in the early stages of embryonic development and plays a significant role in the migration and the differentiation of cells into various types of tissues of an organism. However, tumor cells, with altered form and function, use the EMT process to migrate and invade other tissues in the body. Several experimental (in vivo and in vitro) and clinical trial studies have shown the antitumor activity of crotoxin (CTX), a heterodimeric phospholipase A2 present in the <i>Crotalus durissus terrificus</i> venom. In this study, we show that CTX modulates the microenvironment of tumor cells. We have also evaluated the effect of CTX on the EMT process in the spheroid model. The invasion of type I collagen gels by heterospheroids (mix of MRC-5 and A549 cells constitutively prepared with 12.5 nM CTX), expression of EMT markers, and secretion of MMPs were analyzed. Western blotting analysis shows that CTX inhibits the expression of the mesenchymal markers, N-cadherin, α-SMA, and αv. This study provides evidence of CTX as a key modulator of the EMT process, and its antitumor action can be explored further for novel drug designing against metastatic cancer.Ellen Emi KatoSandra Coccuzzo SampaioMDPI AGarticlecrotoxinepithelial–mesenchymal transitionspheroid modeltumor stromaMedicineRENToxins, Vol 13, Iss 830, p 830 (2021)
institution DOAJ
collection DOAJ
language EN
topic crotoxin
epithelial–mesenchymal transition
spheroid model
tumor stroma
Medicine
R
spellingShingle crotoxin
epithelial–mesenchymal transition
spheroid model
tumor stroma
Medicine
R
Ellen Emi Kato
Sandra Coccuzzo Sampaio
Crotoxin Modulates Events Involved in Epithelial–Mesenchymal Transition in 3D Spheroid Model
description Epithelial–mesenchymal transition (EMT) occurs in the early stages of embryonic development and plays a significant role in the migration and the differentiation of cells into various types of tissues of an organism. However, tumor cells, with altered form and function, use the EMT process to migrate and invade other tissues in the body. Several experimental (in vivo and in vitro) and clinical trial studies have shown the antitumor activity of crotoxin (CTX), a heterodimeric phospholipase A2 present in the <i>Crotalus durissus terrificus</i> venom. In this study, we show that CTX modulates the microenvironment of tumor cells. We have also evaluated the effect of CTX on the EMT process in the spheroid model. The invasion of type I collagen gels by heterospheroids (mix of MRC-5 and A549 cells constitutively prepared with 12.5 nM CTX), expression of EMT markers, and secretion of MMPs were analyzed. Western blotting analysis shows that CTX inhibits the expression of the mesenchymal markers, N-cadherin, α-SMA, and αv. This study provides evidence of CTX as a key modulator of the EMT process, and its antitumor action can be explored further for novel drug designing against metastatic cancer.
format article
author Ellen Emi Kato
Sandra Coccuzzo Sampaio
author_facet Ellen Emi Kato
Sandra Coccuzzo Sampaio
author_sort Ellen Emi Kato
title Crotoxin Modulates Events Involved in Epithelial–Mesenchymal Transition in 3D Spheroid Model
title_short Crotoxin Modulates Events Involved in Epithelial–Mesenchymal Transition in 3D Spheroid Model
title_full Crotoxin Modulates Events Involved in Epithelial–Mesenchymal Transition in 3D Spheroid Model
title_fullStr Crotoxin Modulates Events Involved in Epithelial–Mesenchymal Transition in 3D Spheroid Model
title_full_unstemmed Crotoxin Modulates Events Involved in Epithelial–Mesenchymal Transition in 3D Spheroid Model
title_sort crotoxin modulates events involved in epithelial–mesenchymal transition in 3d spheroid model
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/f6b26b6954c3409d81dd60f24a5c69bd
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AT sandracoccuzzosampaio crotoxinmodulateseventsinvolvedinepithelialmesenchymaltransitionin3dspheroidmodel
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