Artemisinin derivatives are the most effective and safe antimalarial drugs available. They possess anti-angiogenic and antitumor activity as well. We reported that the inhibition of growth and differentiation of endothelial cells (EC) depends on the artemisinin derivative used (D’Alessandro 2007). We extended here these observations by evaluating the role of hypoxia in the response of EC to artemisinins. Hypoxia plays a crucial role both in malaria and tumours and is a potent signal for EC itself. In severe malaria, microvascular occlusion by infected red blood cells generates a hypoxic microenvironment. In cancer, the growth of tumour mass causes a failure in the oxygen and nutrients supply and generates hypoxia. We found that dihydroartemisinin (DHA), the active metabolite of most artemisinins, causes a time and dose-dependent inhibition of EC growth which is influenced by the oxygen tension: at low doses (those found in plasma of malaria patients) DHA is more active in hypoxia, whereas at high doses (those proposed as antiangiogenic and antitumor) it is more effective in normoxia. At high doses DHA induces EC apoptosis and affects the cell cycle via oxidative stress. At low doses cytostasis seems to be present since neither apoptosis nor oxidative stress were detected. The implication of these findings for therapeutic regimens with artemisinins is under discussion. Financial support by EU18834AntiMal is acknowledged

Effect of artemisinin derivatives on endothelial cells: role of hypoxia / S. D’Alessandro, N. Basilico, Y. Corbett, S. Finaurini, M.M. Scaltrito, D. Taramelli. ((Intervento presentato al convegno Spring meeting and trypanosomiasis & leishmaniasis seminar tenutosi a Cardiff nel 2010.

Effect of artemisinin derivatives on endothelial cells: role of hypoxia

S. D’Alessandro
Primo
;
N. Basilico
Secondo
;
Y. Corbett;S. Finaurini;M.M. Scaltrito
Penultimo
;
D. Taramelli
Ultimo
2010

Abstract

Artemisinin derivatives are the most effective and safe antimalarial drugs available. They possess anti-angiogenic and antitumor activity as well. We reported that the inhibition of growth and differentiation of endothelial cells (EC) depends on the artemisinin derivative used (D’Alessandro 2007). We extended here these observations by evaluating the role of hypoxia in the response of EC to artemisinins. Hypoxia plays a crucial role both in malaria and tumours and is a potent signal for EC itself. In severe malaria, microvascular occlusion by infected red blood cells generates a hypoxic microenvironment. In cancer, the growth of tumour mass causes a failure in the oxygen and nutrients supply and generates hypoxia. We found that dihydroartemisinin (DHA), the active metabolite of most artemisinins, causes a time and dose-dependent inhibition of EC growth which is influenced by the oxygen tension: at low doses (those found in plasma of malaria patients) DHA is more active in hypoxia, whereas at high doses (those proposed as antiangiogenic and antitumor) it is more effective in normoxia. At high doses DHA induces EC apoptosis and affects the cell cycle via oxidative stress. At low doses cytostasis seems to be present since neither apoptosis nor oxidative stress were detected. The implication of these findings for therapeutic regimens with artemisinins is under discussion. Financial support by EU18834AntiMal is acknowledged
Settore MED/04 - Patologia Generale
British society for parasitology
Effect of artemisinin derivatives on endothelial cells: role of hypoxia / S. D’Alessandro, N. Basilico, Y. Corbett, S. Finaurini, M.M. Scaltrito, D. Taramelli. ((Intervento presentato al convegno Spring meeting and trypanosomiasis & leishmaniasis seminar tenutosi a Cardiff nel 2010.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/166668
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