LQFM030 reduced Ehrlich ascites tumor cell proliferation and VEGF levels.

Abstract

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 150mg/kg) for 10days 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>2000-5000mg/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.

• Authors: Mariana Flavia da Mota, Flávio Silva de Carvalho, Renato Ivan de Ávila, Paulo Henrique Marcelino de Ávila, Alane Pereira Cortez, Ricardo Menegatti, José Ricardo Sabino, Thais Rosa Marques Dos Santos, Sandro Antônio Gomes, Luiz Carlos da Cunha, Marize Campos Valadares
• Journal: Life sciences (Life Sci) Vol. 201 Pg. 1-8 (May 15 2018) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 29278686 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier Inc.

Chemical References

• Angiogenesis Inhibitors
• LQFM030
• Piperidines
• Pyrazoles
• Tumor Suppressor Protein p53
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Caspases
• Oncogene Protein p21(ras)

Topics

• Angiogenesis Inhibitors (pharmacology, toxicity)
• Animals
• Apoptosis (drug effects)
• Carcinoma, Ehrlich Tumor (drug therapy, pathology)
• Caspases (biosynthesis)
• Cell Proliferation (drug effects)
• Female
• Injections, Intraperitoneal
• Male
• Mice
• Neovascularization, Pathologic (drug therapy, pathology)
• Oncogene Protein p21(ras) (biosynthesis, genetics)
• Piperidines (pharmacology, toxicity)
• Pyrazoles (pharmacology, toxicity)
• Tumor Suppressor Protein p53 (biosynthesis, genetics)
• Vascular Endothelial Growth Factor A (biosynthesis)