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, 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.
Laboratório de Genética Toxicológica, Departamento de Biologia Geral, Universidade Estadual de Londrina, Londrina, PR, Brazil.
Leonardo Campos
LC
Zanelatto
Laboratório de Genética Toxicológica, Departamento de Biologia Geral, Universidade Estadual de Londrina, Londrina, PR, Brazil.
Patrícia Benites Gonçalves da
PB
Silva
Laboratório de Genética Toxicológica, Departamento de Biologia Geral, Universidade Estadual de Londrina, Londrina, PR, Brazil.
Daniele
D
Sartori
Laboratório de Fisiologia de Radicais Livres, Departamento de Patologia, Universidade Estadual de Londrina, Londrina, PR, Brazil.
Carolina
C
Panis
Laboratório de Genética Toxicológica, Departamento de Biologia Geral, Universidade Estadual de Londrina, Londrina, PR, Brazil.
Sandra
S
Lepri
Grupo de Estudos em Química Orgânica e Biológica, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Ângelo de
Âd
Fátima
Laboratório de Genética Toxicológica, Departamento de Biologia Geral, Universidade Estadual de Londrina, Londrina, PR, Brazil.
Mário Sérgio
MS
Mantovani