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LNO3和L3与肝癌细胞的抗增殖和促凋亡作用相关。

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

作者信息

Zanelatto Leonardo Campos, Silva Patrícia Benites Gonçalves da, Sartori Daniele, Panis Carolina, Lepri Sandra, Fátima Ângelo de, Mantovani Mário Sérgio

机构信息

Laboratório de Genética Toxicológica, Departamento de Biologia Geral, Universidade Estadual de Londrina, Londrina, PR, Brazil.

Laboratório de Fisiologia de Radicais Livres, Departamento de Patologia, Universidade Estadual de Londrina, Londrina, PR, Brazil.

出版信息

Genet Mol Biol. 2016 Apr-Jun;39(2):270-8. doi: 10.1590/1678-4685-GMB-2015-0184.

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.

摘要

抗肿瘤物质的鉴定是生物医学研究的重点。沙利度胺的两种结构类似物LNO3和L3是两种可能具有此类抗肿瘤特性的合成化合物。我们评估了这些物质的毒理学效应,包括对HTC细胞的细胞毒性、遗传毒性和凋亡诱导作用。此外,还研究了自由基(一氧化氮和超氧化物)的产生,并通过RT-qPCR测定了半胱天冬酶基因3、8和9的表达。这些化合物表现出细胞毒性作用,导致细胞增殖受到抑制。在所有试验中,LNO3比L3更有效且毒性更大。LNO3刺激了NO和超氧化物的释放,同时伴有过氧亚硝酸盐的形成。两种化合物均以剂量依赖的方式诱导凋亡;然而,半胱天冬酶3、8和9的表达没有变化。这些结果表明,L3和LNO3在HTC细胞中具有抗增殖和促凋亡作用。此外,尽管L3和LNO3表现出细胞毒性,但它们可能是肿瘤治疗研究中有用的辅助剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c48d/4910562/524eb7cb1b43/1415-4757-gmb-39-02-0270-gf01.jpg

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