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Published on: July 20, 2019
LNO3 AND L3 Are Associated With Antiproliferative And Pro-Apoptotic Action In Hepatoma Cells
Leonardo Campos Zanelatto1, Patrícia Benites Gonçalves da Silva1, Daniele Sartori1
1Laboratório de Genética Toxicológica, Departamento de Biologia Geral, Universidade Estadual de Londrina, Londrina, PR, Brazil.
Abstract:
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.
Insights
Two thalidomide analogues, LNO3 and L3, show potential as antitumor agents. They inhibit cancer cell proliferation and induce apoptosis, with LNO3 being more potent, suggesting their use in cancer therapy.
Area of Science:
- Biomedical research
- Drug discovery
- Toxicology
Background:
- Thalidomide analogues are investigated for antitumoral properties.
- LNO3 and L3 are synthetic compounds with potential anticancer effects.
- Understanding their toxicological profile is crucial for therapeutic development.
Purpose of the Study:
- To evaluate the toxicological effects of LNO3 and L3 on HTC cells.
- To assess the induction of cytotoxicity, genotoxicity, and apoptosis.
- To investigate the production of free radicals and expression of key apoptosis-related genes.
Main Methods:
- Cytotoxicity and genotoxicity assays were performed on HTC cells.
- Apoptosis induction was measured.
- Nitric oxide (NO) and superoxide production were quantified.
- Caspase gene expression (3, 8, 9) was analyzed using RT-qPCR.
Main Results:
- Both LNO3 and L3 inhibited HTC cell proliferation, demonstrating cytotoxic effects.
- LNO3 exhibited greater efficacy and toxicity compared to L3.
- LNO3 stimulated nitric oxide and superoxide release, leading to peroxynitrite formation.
- Apoptosis was induced by both compounds in a dose-dependent manner, but caspase gene expression remained unchanged.
Conclusions:
- L3 and LNO3 demonstrate antiproliferative and pro-apoptotic effects in HTC cells.
- Despite exhibiting cytotoxicity, these compounds may serve as valuable coadjuvants in cancer treatment research.
- Further studies are warranted to explore their therapeutic potential and optimize their application.
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