Inhibition of angiogenesis in vivo and growth of Kaposi's sarcoma xenograft tumors by the anti-malarial artesunate.
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.
Dell'Eva
Raffaella
R
Molecular Oncology, National Cancer Research Institute (IST), Largo Rosanna Benzi 10, 16132 Genova, Italy.
Pfeffer
Ulrich
U
Vené
Roberta
R
Anfosso
Luca
L
Forlani
Alessandra
A
Albini
Adriana
A
Efferth
Thomas
T
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D003094:Collagen / Q000187:drug effects; D004195:Disease Models, Animal; D004338:Drug Combinations; D007797:Laminin / Q000187:drug effects; D008297:Male; D045726:Metalloproteases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011509:Proteoglycans / Q000187:drug effects; D012514:Sarcoma, Kaposi / Q000188:drug therapy*; D012717:Sesquiterpenes / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000962:Antimalarials; D000970:Antineoplastic Agents; D037621:Artemisinins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D012717:Sesquiterpenes; C059485:matrigel; D000077332:Artesunate; D003094:Collagen; D045726:Metalloproteases