Targeting different angiogenic pathways with combination of curcumin, leflunomide and perindopril inhibits diethylnitrosamine-induced hepatocellular carcinoma in mice

No effective chemopreventive agent has been approved against hepatocellular carcinoma (HCC) to date. Since HCC is one of the hypervascular solid tumors, blocking angiogenesis represents an intriguing approach to HCC chemoprevention. The aim of the current study was to examine the combined effect of...

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Bibliographic Details
Published in:European journal of pharmacology 2014-01, Vol.723, p.267-275
Main Authors: Nasr, Magda, Selima, Eman, Hamed, Omar, Kazem, Amany
Format: Article
Language:English
Subjects:
Angiogenesis
Angiotensin-Converting Enzyme Inhibitors - therapeutic use
Animals
Antineoplastic Agents - therapeutic use
Antirheumatic Agents - therapeutic use
Carcinogens
Carcinoma, Hepatocellular - chemically induced
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Chemoprevention
Curcumin
Curcumin - therapeutic use
Diethylnitrosamine
Drug Therapy, Combination
Hepatocellular carcinoma
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Isoxazoles - therapeutic use
Leflunomide
Liver - drug effects
Liver - metabolism
Liver - pathology
Liver Neoplasms - chemically induced
Liver Neoplasms - drug therapy
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Male
Mice
Neovascularization, Pathologic - drug therapy
Neovascularization, Pathologic - metabolism
Neovascularization, Pathologic - pathology
Perindopril
Perindopril - therapeutic use
Platelet Endothelial Cell Adhesion Molecule-1 - metabolism
Vascular Endothelial Growth Factor A - metabolism
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Summary:No effective chemopreventive agent has been approved against hepatocellular carcinoma (HCC) to date. Since HCC is one of the hypervascular solid tumors, blocking angiogenesis represents an intriguing approach to HCC chemoprevention. The aim of the current study was to examine the combined effect of the anti-angiogenic agents: leflunomide; a disease modifying antirheumatic drug, perindopril; an angiotensin converting enzyme inhibitor (ACEI) and curcumin; the active principle of turmeric, on diethylnitrosamine (DEN)-induced HCC in mice. Eight weeks following DEN administration, there was a significant rise in immunohistochemical staining of CD31-positive endothelial cells and consequently hepatic microvessel density (MVD) as compared to normal liver. DEN treatment was associated with elevation in hepatic vascular endothelial growth factor (VEGF) level as compared to normal controls (P
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2013.11.022