Anti-Angiogenic and Anti-Inflammatory Effects of Statins: Relevance to Anti-Cancer Therapy

Authors: Dulak, Jozef¹; Jozkowicz, Alicja¹

Source: Current Cancer Drug Targets, Volume 5, Number 8, December 2005 , pp. 579-594(16)

Publisher: Bentham Science Publishers

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Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes, genes.
Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cancer.
As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.

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Abstract:

Angiogenesis is indispensable for the growth of solid tumors and angiogenic factors are also involved in the progression of hematological malignancies. Targeting the formation of blood vessels is therefore regarded as a promising strategy in cancer therapy. Interestingly, besides demonstration of some beneficial effects of novel anti-angiogenic compounds, recent data on the activity of already available drugs point to their potential application in anti-angiogenic therapy. Among these are the statins, the inhibitors of 3- hydroxy-3-methylglutaryl-coenzyme A reductase. Statins are very efficient in the treatment of hypercholesterolemia in cardiovascular disorders; however, their effects are pleiotropic and some are not directly related to the inhibition of cholesterol synthesis. Some reports particularly highlight the proangiogenic effects of statins, which are caused by low, nanomolar concentrations and are regarded as beneficial for the treatment of cardiovascular diseases. On the other hand, the anti-angiogenic activities, observed at micromolar concentrations of statins, may be of special significance for cancer therapy. Those effects are caused by the inhibition of both proliferation and migration and induction of apoptosis in endothelial cells. Moreover, the statin-mediated inhibition of vascular endothelial growth factor synthesis, the major angiogenic mediator, may contribute to the attenuation of angiogenesis.

It has been suggested that the anti-cancer effect of statins can be potentially exploited for the cancer therapy. However, several clinical trials aimed at the inhibition of tumor growth by treatment with very high doses of statins did not provide conclusive data. Herein, the reasons for those outcomes are discussed and the rationale for further studies is presented.

Keywords: Vascular endothelial growth factor; 3-hydroxy-3-methylglutaryl-coenzyme A reductase; nitric oxide; heme oxygenase; apoptosis; endothelium; atherosclerosis; hypercholesterolemia

Document Type: Review article

DOI: 10.2174/156800905774932824

Affiliations: 1: Department of Medical Biotechnology, Faculty of Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.