Paper Information

Title: 

BIPHASIC EFFECTS OF ATORVASTATIN ON ANGIOGENESIS: RELEVANCE TO CANCER

Type: PAPER
Author(s): GARJANI A.R.*,REZAZADEH H.,ANDALIB S.,ZIAEI M.,MALEKI N.
 
 *DEPARTMENT OF PHARMACOLOGY, SCHOOL OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2007Volume 18
 
 
Abstract: 

Angiogenesis is a major pathological component of disease such as cancer and coronary heart disease. The stimulation of angiogenesis regarded as an encouraging strategy in treating coronary artery disease and its blocking is effective for treating malignancy. Statins have been shown to exert 'pleiotropic effects' independent of their cholesterol lowering action. Whether, all of these effects dependent on mevalonate pathway must be answered. With respect to angiogenesis, some reports show that statins promote collateral vessel formation in ischemic tissue of animal models. On the other hand, the same drugs reportedly interrupted angiogenesis. More recent reports indicate a biphasic effect of statins on angiogenesis in cultured endothelial cells in a dose dependent manner. However, consensus on these effects has not yet been reached. A growing body of preclinical data indicates that statins may have antineoplastic properties, but some studies raise the possibility that statins may possess a carcinogenic potential. We found that in mice and rat air-pouch models of local inflammation, oral administration of atorvastatin produced anti-inflammatory effects, where locally injection of the drug into the pouch caused a significant pro-angiogenic and pro-inflammatory effects. Contrary to pro-angiogenic effect of locally administrated drug, the anti-inflammatory effect of oral atorvastatin was prevented by mevalonate. The results indicate the involvement of mevalonate pathway in the anti-inflammatory actions of orally used statins. We also showed that high doses of atorvastatin augmented croton oil induced skin tumors in mice. It is suggested that pro-angiogenic effect of the drug which can be a reason for the skin tumors promotion, is independent of HMG-CoA reductase inhibition and can be mediated directly by atorvastatin.

 
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