LQFM030 reduced Ehrlich ascites tumor cell proliferation and VEGF levels

Mota, Mariana Flavia da; Carvalho, Flávio Silva de; Marcelino, Renato Ivan de Ávila; Ávila, Paulo Henrique Marcelino de; Cortez, Alane Pereira; Menegatti, Ricardo; Sabino, José Ricardo; Santos, Thais Rosa Marques dos; Gomes, Sandro Antônio; Cunha, Luiz Carlos da

LQFM030 reduced Ehrlich ascites tumor cell proliferation and VEGF levels

Data

2018

Autores

Mota, Mariana Flavia da

Carvalho, Flávio Silva de

Marcelino, Renato Ivan de Ávila

Ávila, Paulo Henrique Marcelino de

Cortez, Alane Pereira

Menegatti, Ricardo

Sabino, José Ricardo

Santos, Thais Rosa Marques dos

Gomes, Sandro Antônio

Cunha, Luiz Carlos da

Resumo

Aims: This study reports the biological properties of LQFM030 in vivo, a molecular simplification of the compound nutlin-1. Main methods: Ehrlich ascites tumor (EAT)-bearing mice were treated intraperitoneally with LQFM030 (50, 75 or 150 mg/kg) for 10 days to determine changes in ascites tumor volume, body weight, cytotoxicity and angiogenesis. Moreover, flow cytometric expression of p53 and p21 proteins and caspase-3/7, −8 and −9 activation were investigated in EAT cells from mice treated. Acute oral systemic toxicity potential of LQFM030 in mice was also investigated using an alternative method. Key findings: Treatment of EAT-bearing mice with LQFM030 resulted in a marked decline in tumor cell proliferation and the vascular endothelial growth factor (VEGF) levels along with enhanced survival of the mice. Apoptotic tumor cell death was detected through p53 and p21 modulation and increase of caspase-3/7, −8 and −9 activity. LQFM030 also showed orally well tolerated, being classified in the UN GHS category 5 (LD50 > 2000–5000 mg/Kg). Significance: LQFM030 seems to be a promising antitumor candidate for combinatory therapy with typical cytotoxic compounds, reducing the toxicity burden while allowing a superior anticancer activity. Moreover, these data also open new perspectives for LQFM030 as an antiangiogenic agent for treatment of diseases involving VEGF overexpression.

Palavras-chave

Ehrlich ascites tumor, Nutlins, VEGF, MDM2 inhibitors, p53, p21

Citação

MOTA, Mariana Flavia da et al. LQFM030 reduced Ehrlich ascites tumor cell proliferation and VEGF levels. Life Sciences, Oxford, v. 201, p. 1-8, 2017. DOI: 10.1016/j.lfs.2017.12.029. Disponível em: https://www.sciencedirect.com/science/article/pii/S0024320517306768?via%3Dihub. Acesso em: 22 jan. 2024.