TY - JOUR
T1 - Inhibition of angiogenesis in vivo and growth of Kaposi's sarcoma xenograft tumors by the anti-malarial artesunate
AU - Dell'Eva, Raffaella
AU - Pfeffer, Ulrich
AU - Vené, Roberta
AU - Anfosso, Luca
AU - Forlani, Alessandra
AU - Albini, Adriana
AU - Efferth, Thomas
PY - 2004/12/15
Y1 - 2004/12/15
N2 - Artesunate (ART) is a semi-synthetic derivative of the sesquiterpene artemisinin used for the second line therapy of malaria infections with Plasmodium falciparum. ART also inhibits growth of many transformed cell lines. In the present investigation, we show that ART inhibited the growth of normal human umbilical endothelial cells and of KS-IMM cells that we have established from a Kaposi's sarcoma lesion obtained from a renal transplant patient. The growth inhibitory activity correlated with the induction of apoptosis in KS-IMM cells. Apoptosis was not observed in normal endothelial cells, which, however, showed drastically increased cell doubling times upon ART treatment. ART strongly reduced angiogenesis in vivo in terms of vascularization of Matrigel plugs injected subcutaneously into syngenic mice. We conclude that ART represents a promising candidate drug for the treatment of the highly angiogenic Kaposi's sarcoma. As a low-cost drug, it might be of particular interest for areas of Kaposi's sarcoma endemics. ART could be useful for the prevention of tumor angiogenesis.
AB - Artesunate (ART) is a semi-synthetic derivative of the sesquiterpene artemisinin used for the second line therapy of malaria infections with Plasmodium falciparum. ART also inhibits growth of many transformed cell lines. In the present investigation, we show that ART inhibited the growth of normal human umbilical endothelial cells and of KS-IMM cells that we have established from a Kaposi's sarcoma lesion obtained from a renal transplant patient. The growth inhibitory activity correlated with the induction of apoptosis in KS-IMM cells. Apoptosis was not observed in normal endothelial cells, which, however, showed drastically increased cell doubling times upon ART treatment. ART strongly reduced angiogenesis in vivo in terms of vascularization of Matrigel plugs injected subcutaneously into syngenic mice. We conclude that ART represents a promising candidate drug for the treatment of the highly angiogenic Kaposi's sarcoma. As a low-cost drug, it might be of particular interest for areas of Kaposi's sarcoma endemics. ART could be useful for the prevention of tumor angiogenesis.
KW - Angiogenesis
KW - Apoptosis
KW - Drug resistance
KW - Kaposi's sarcoma
UR - http://www.scopus.com/inward/record.url?scp=8844258698&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=8844258698&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2004.08.021
DO - 10.1016/j.bcp.2004.08.021
M3 - Article
C2 - 15548382
AN - SCOPUS:8844258698
VL - 68
SP - 2359
EP - 2366
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 12
ER -