Coumarin derivative 7-isopentenyloxycoumarin induces in vivo antitumor activity by inhibit angiogenesis via CCL2 chemokine decrease
| Autor: | Rodrigo Santos Aquino de Araújo, Robson Cavalcante Veras, Vivianne Mendes Mangueira, Leônia Maria Batista, Ryldene Marques Duarte da Cruz, Francisco Jaime Bezerra Mendonça, Jephesson Alex Floriano dos Santos, Tatyanna Kelvia Gomes de Sousa, Tatianne Mota Batista, Marianna Vieira Sobral, Renata Albuquerque de Abrantes, Giciane Carvalho Vieira, Fagner Carvalho Leite, Rafael Carlos Ferreira, Monalisa Taveira Brito |
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| Rok vydání: | 2019 |
| Předmět: |
Angiogenesis
Down-Regulation Angiogenesis Inhibitors Pharmacology Ehrlich ascites carcinoma 03 medical and health sciences Mice 0302 clinical medicine In vivo Coumarins medicine Tumor Microenvironment Animals Carcinoma Ehrlich Tumor Chemokine CCL2 030304 developmental biology 0303 health sciences Neovascularization Pathologic Chemistry Lethal dose General Medicine medicine.disease Acute toxicity Hemolysis 030220 oncology & carcinogenesis Toxicity Cancer cell Female Microvascular Density Signal Transduction |
| Zdroj: | Naunyn-Schmiedeberg's archives of pharmacology. 393(9) |
| ISSN: | 1432-1912 |
| Popis: | Cancer is one of the most urgent problems in medicine. In recent years, cancer is the second leading cause of death globally. In search for more effective and less toxic treatment against cancer, natural products are used as prototypes in the synthesis of new anticancer drugs. The aim of this study was to investigate the in vivo toxicity and the mechanism of antitumor action of 7-isopentenyloxycoumarin (UMB-07), a coumarin derivative with antitumor activity. The toxicity was evaluated in vitro (hemolysis assay), and in vivo (micronucleus and acute toxicity assays). Ehrlich ascites carcinoma model was used to evaluate in vivo antitumor activity of UMB-07 (12.5, 25, or 50 mg/kg, intraperitoneally, i.p.), after 9 days of treatment, as well as toxicity. UMB-07 (2000 μg/mL) induced only 0.8% of hemolysis in peripheral blood erythrocytes of mice. On acute toxicity assay, LD50 (50% lethal dose) was estimated at around 1000 mg/kg (i.p.), and no micronucleated erythrocytes were recorded after UMB-07 (300 mg/kg, i.p.) treatment. UMB-07 (25 and 50 mg/kg) reduced tumor volume and total viable cancer cells. In the mechanism action investigation, no changes were observed on the cell cycle analysis; however, UMB-07 reduced peritumoral microvessels density and CCL2 chemokine levels. In addition, UMB-07 showed weak toxicity on biochemical, hematological, and histological parameters after 9 days of antitumor treatment. The current findings suggest that UMB-07 has low toxicity and exerts antitumor effect by inhibit angiogenesis via CCL2 chemokine decrease. |
| Databáze: | OpenAIRE |
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