Nelfinavir induces TRAIL receptor upregulation in ovarian cancer cells.
HIV protease inhibitors are currently being discussed to be useful as new and alternative anti-cancer agents, especially as second line treatments for chemo-resistant human cancer types. Among three clinically applied HIV protease inhibitors tested, we found a high efficacy of nelfinavir on ovarian cancer cells, accompanied by apoptosis (annexin binding) and necrosis (propidium iodide permeability). In vitro, at concentrations used to induce cell death in ovarian cancer cells, nelfinavir had no effect on the cellular viability of fibroblasts or peripheral blood mononuclear leukocytes. Nelfinavir sensitized ovarian cancer cells to treatment with an apoptosis-inducing TRAIL receptor antibody due to upregulation of the TRAIL receptor DR5 as shown by RT-PCR and FACScan analysis. We conclude that nelfinavir, an already approved drug, is a highly efficient agent against ovarian cancer cells and could sensitize ovarian cancer cells to TRAIL treatment, either therapeutically applied or endogenously produced by cells of the immune system.
Brüning
Ansgar
A
University Hospital Munich, Department of Obstetrics/Gynecology, Maistrasse 11, 80337 Munich, Germany. ansgar.bruening@med.uni-muenchen.de
Vogel
Marianne
M
Burger
Petra
P
Rahmeh
Martina
M
Gingelmaier
Andrea
A
Friese
Klaus
K
Lenhard
Miriam
M
Burges
Alexander
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D005260:Female; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D019888:Nelfinavir / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D000970:Antineoplastic Agents; D017320:HIV Protease Inhibitors; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D019888:Nelfinavir