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LNO3 AND L3 Are Associated With Antiproliferative And Pro-Apoptotic Action In Hepatoma Cells

The identification of antitumoral substances is the focus of intense biomedical research. Two structural analogues of thalidomide, LNO3 and L3, are two synthetic compounds that might possess such antitumor properties. We evaluated the toxicological effects of these substances, including cytotoxicity...

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Autores principales: Zanelatto, Leonardo Campos, da Silva, Patrícia Benites Gonçalves, Sartori, Daniele, Panis, Carolina, Lepri, Sandra, de Fátima, Ângelo, Mantovani, Mário Sérgio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Sociedade Brasileira de Genética 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910562/
https://www.ncbi.nlm.nih.gov/pubmed/27303908
http://dx.doi.org/10.1590/1678-4685-GMB-2015-0184
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author Zanelatto, Leonardo Campos
da Silva, Patrícia Benites Gonçalves
Sartori, Daniele
Panis, Carolina
Lepri, Sandra
de Fátima, Ângelo
Mantovani, Mário Sérgio
author_facet Zanelatto, Leonardo Campos
da Silva, Patrícia Benites Gonçalves
Sartori, Daniele
Panis, Carolina
Lepri, Sandra
de Fátima, Ângelo
Mantovani, Mário Sérgio
author_sort Zanelatto, Leonardo Campos
collection PubMed
description The identification of antitumoral substances is the focus of intense biomedical research. Two structural analogues of thalidomide, LNO3 and L3, are two synthetic compounds that might possess such antitumor properties. We evaluated the toxicological effects of these substances, including cytotoxicity, genotoxicity and induction of apoptosis in HTC cells. Additionally, the production of free radicals (nitric oxide and superoxide) was investigated, and the expression of caspases genes 3, 8, and 9 were determined by RT-qPCR. The compounds exhibited cytotoxic effects that resulted in inhibited cell proliferation. LNO3 showed to be more effective and toxic than L3 in all assays. LNO3 stimulated the release of NO and superoxide, which was accompanied by the formation of peroxynitrite. Apoptosis was induced in a dose-dependent manner by both compounds; however, the expression of caspases 3, 8 and 9 was unchanged. These results suggested that L3 and LNO3 possess antiproliferative and pro-apoptotic effects in HTC cells. Additionally, although they exhibited cytotoxicity, L3 and LNO3 might be useful coadjuvants in tumor treatment studies.
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spelling pubmed-49105622016-07-01 LNO3 AND L3 Are Associated With Antiproliferative And Pro-Apoptotic Action In Hepatoma Cells Zanelatto, Leonardo Campos da Silva, Patrícia Benites Gonçalves Sartori, Daniele Panis, Carolina Lepri, Sandra de Fátima, Ângelo Mantovani, Mário Sérgio Genet Mol Biol Mutagenesis The identification of antitumoral substances is the focus of intense biomedical research. Two structural analogues of thalidomide, LNO3 and L3, are two synthetic compounds that might possess such antitumor properties. We evaluated the toxicological effects of these substances, including cytotoxicity, genotoxicity and induction of apoptosis in HTC cells. Additionally, the production of free radicals (nitric oxide and superoxide) was investigated, and the expression of caspases genes 3, 8, and 9 were determined by RT-qPCR. The compounds exhibited cytotoxic effects that resulted in inhibited cell proliferation. LNO3 showed to be more effective and toxic than L3 in all assays. LNO3 stimulated the release of NO and superoxide, which was accompanied by the formation of peroxynitrite. Apoptosis was induced in a dose-dependent manner by both compounds; however, the expression of caspases 3, 8 and 9 was unchanged. These results suggested that L3 and LNO3 possess antiproliferative and pro-apoptotic effects in HTC cells. Additionally, although they exhibited cytotoxicity, L3 and LNO3 might be useful coadjuvants in tumor treatment studies. Sociedade Brasileira de Genética 2016 /pmc/articles/PMC4910562/ /pubmed/27303908 http://dx.doi.org/10.1590/1678-4685-GMB-2015-0184 Text en Copyright © 2016, Sociedade Brasileira de Genética. http://creativecommons.org/licenses/by/4.0/ License information: This is an open-access article distributed under the terms of the Creative Commons Attribution License (type CC-BY), which permits unrestricted use, distribution and reproduction in any medium, provided the original article is properly cited.
spellingShingle Mutagenesis
Zanelatto, Leonardo Campos
da Silva, Patrícia Benites Gonçalves
Sartori, Daniele
Panis, Carolina
Lepri, Sandra
de Fátima, Ângelo
Mantovani, Mário Sérgio
LNO3 AND L3 Are Associated With Antiproliferative And Pro-Apoptotic Action In Hepatoma Cells
title LNO3 AND L3 Are Associated With Antiproliferative And Pro-Apoptotic Action In Hepatoma Cells
title_full LNO3 AND L3 Are Associated With Antiproliferative And Pro-Apoptotic Action In Hepatoma Cells
title_fullStr LNO3 AND L3 Are Associated With Antiproliferative And Pro-Apoptotic Action In Hepatoma Cells
title_full_unstemmed LNO3 AND L3 Are Associated With Antiproliferative And Pro-Apoptotic Action In Hepatoma Cells
title_short LNO3 AND L3 Are Associated With Antiproliferative And Pro-Apoptotic Action In Hepatoma Cells
title_sort lno3 and l3 are associated with antiproliferative and pro-apoptotic action in hepatoma cells
topic Mutagenesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910562/
https://www.ncbi.nlm.nih.gov/pubmed/27303908
http://dx.doi.org/10.1590/1678-4685-GMB-2015-0184
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