Cargando…

The SOD Mimic MnTnHex-2-PyP(5+) Reduces the Viability and Migration of 786-O Human Renal Cancer Cells

Clear-cell renal carcinoma (ccRCC) is the most common type of renal cancer. The importance of oxidative stress in the context of this disease has been described, although there is only little information concerning the role of superoxide dismutase (SOD) enzymes. The importance of SOD in different pa...

Descripción completa

Detalles Bibliográficos
Autores principales: Costa, João G., Saraiva, Nuno, Batinic-Haberle, Ines, Castro, Matilde, Oliveira, Nuno G., Fernandes, Ana S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826590/
https://www.ncbi.nlm.nih.gov/pubmed/31627290
http://dx.doi.org/10.3390/antiox8100490
_version_ 1783465124054433792
author Costa, João G.
Saraiva, Nuno
Batinic-Haberle, Ines
Castro, Matilde
Oliveira, Nuno G.
Fernandes, Ana S.
author_facet Costa, João G.
Saraiva, Nuno
Batinic-Haberle, Ines
Castro, Matilde
Oliveira, Nuno G.
Fernandes, Ana S.
author_sort Costa, João G.
collection PubMed
description Clear-cell renal carcinoma (ccRCC) is the most common type of renal cancer. The importance of oxidative stress in the context of this disease has been described, although there is only little information concerning the role of superoxide dismutase (SOD) enzymes. The importance of SOD in different pathological conditions promoted the development of SOD mimics (SODm). As such, manganese(III) porphyrins can mimic the natural SOD enzymes and scavenge different reactive oxygen species (ROS), thus modulating the cellular redox status. In this study, the exposure of 786-O human renal cancer cells to MnTnHex-2-PyP(5+) (MnP), a very promising SODm, led to a concentration and time-dependent decrease in cell viability and in the cell proliferation indices, as well as to an increase in apoptosis. No relevant effects in terms of micronuclei formation were observed. Moreover, the exposure to MnP resulted in a concentration-dependent increase in intracellular ROS, presumably due to the generation of H(2)O(2) by the inherent redox mechanisms of MnP, along with the limited ability of cancer cells to detoxify this species. Although the MnP treatment did not result in a reduction in the collective cell migration, a significant decrease in chemotactic migration was observed. Overall, these results suggest that MnP has a beneficial impact on reducing renal cancer cell viability and migration and warrant further studies regarding SODm-based therapeutic strategies against human renal cancer.
format Online
Article
Text
id pubmed-6826590
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-68265902019-11-18 The SOD Mimic MnTnHex-2-PyP(5+) Reduces the Viability and Migration of 786-O Human Renal Cancer Cells Costa, João G. Saraiva, Nuno Batinic-Haberle, Ines Castro, Matilde Oliveira, Nuno G. Fernandes, Ana S. Antioxidants (Basel) Article Clear-cell renal carcinoma (ccRCC) is the most common type of renal cancer. The importance of oxidative stress in the context of this disease has been described, although there is only little information concerning the role of superoxide dismutase (SOD) enzymes. The importance of SOD in different pathological conditions promoted the development of SOD mimics (SODm). As such, manganese(III) porphyrins can mimic the natural SOD enzymes and scavenge different reactive oxygen species (ROS), thus modulating the cellular redox status. In this study, the exposure of 786-O human renal cancer cells to MnTnHex-2-PyP(5+) (MnP), a very promising SODm, led to a concentration and time-dependent decrease in cell viability and in the cell proliferation indices, as well as to an increase in apoptosis. No relevant effects in terms of micronuclei formation were observed. Moreover, the exposure to MnP resulted in a concentration-dependent increase in intracellular ROS, presumably due to the generation of H(2)O(2) by the inherent redox mechanisms of MnP, along with the limited ability of cancer cells to detoxify this species. Although the MnP treatment did not result in a reduction in the collective cell migration, a significant decrease in chemotactic migration was observed. Overall, these results suggest that MnP has a beneficial impact on reducing renal cancer cell viability and migration and warrant further studies regarding SODm-based therapeutic strategies against human renal cancer. MDPI 2019-10-17 /pmc/articles/PMC6826590/ /pubmed/31627290 http://dx.doi.org/10.3390/antiox8100490 Text en © 2019 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/).
spellingShingle Article
Costa, João G.
Saraiva, Nuno
Batinic-Haberle, Ines
Castro, Matilde
Oliveira, Nuno G.
Fernandes, Ana S.
The SOD Mimic MnTnHex-2-PyP(5+) Reduces the Viability and Migration of 786-O Human Renal Cancer Cells
title The SOD Mimic MnTnHex-2-PyP(5+) Reduces the Viability and Migration of 786-O Human Renal Cancer Cells
title_full The SOD Mimic MnTnHex-2-PyP(5+) Reduces the Viability and Migration of 786-O Human Renal Cancer Cells
title_fullStr The SOD Mimic MnTnHex-2-PyP(5+) Reduces the Viability and Migration of 786-O Human Renal Cancer Cells
title_full_unstemmed The SOD Mimic MnTnHex-2-PyP(5+) Reduces the Viability and Migration of 786-O Human Renal Cancer Cells
title_short The SOD Mimic MnTnHex-2-PyP(5+) Reduces the Viability and Migration of 786-O Human Renal Cancer Cells
title_sort sod mimic mntnhex-2-pyp(5+) reduces the viability and migration of 786-o human renal cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826590/
https://www.ncbi.nlm.nih.gov/pubmed/31627290
http://dx.doi.org/10.3390/antiox8100490
work_keys_str_mv AT costajoaog thesodmimicmntnhex2pyp5reducestheviabilityandmigrationof786ohumanrenalcancercells
AT saraivanuno thesodmimicmntnhex2pyp5reducestheviabilityandmigrationof786ohumanrenalcancercells
AT batinichaberleines thesodmimicmntnhex2pyp5reducestheviabilityandmigrationof786ohumanrenalcancercells
AT castromatilde thesodmimicmntnhex2pyp5reducestheviabilityandmigrationof786ohumanrenalcancercells
AT oliveiranunog thesodmimicmntnhex2pyp5reducestheviabilityandmigrationof786ohumanrenalcancercells
AT fernandesanas thesodmimicmntnhex2pyp5reducestheviabilityandmigrationof786ohumanrenalcancercells
AT costajoaog sodmimicmntnhex2pyp5reducestheviabilityandmigrationof786ohumanrenalcancercells
AT saraivanuno sodmimicmntnhex2pyp5reducestheviabilityandmigrationof786ohumanrenalcancercells
AT batinichaberleines sodmimicmntnhex2pyp5reducestheviabilityandmigrationof786ohumanrenalcancercells
AT castromatilde sodmimicmntnhex2pyp5reducestheviabilityandmigrationof786ohumanrenalcancercells
AT oliveiranunog sodmimicmntnhex2pyp5reducestheviabilityandmigrationof786ohumanrenalcancercells
AT fernandesanas sodmimicmntnhex2pyp5reducestheviabilityandmigrationof786ohumanrenalcancercells