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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2021
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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) |
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crotoxin epithelial–mesenchymal transition spheroid model tumor stroma Medicine R |
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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 |
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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 |
work_keys_str_mv |
AT ellenemikato crotoxinmodulateseventsinvolvedinepithelialmesenchymaltransitionin3dspheroidmodel AT sandracoccuzzosampaio crotoxinmodulateseventsinvolvedinepithelialmesenchymaltransitionin3dspheroidmodel |
_version_ |
1718410254839971840 |