Lentiviral delivery of HIV-1 Vpr protein induces apoptosis in transformed cells.
Most current anticancer therapies act by inducing tumor cell stasis followed by apoptosis. HIV-1 Vpr effectively induces apoptosis of T cells after arrest of cells at a G(2)/M checkpoint. Here, we investigated whether this property of Vpr could be exploited for use as a potential anticancer agent. As a potentially safer alternative to transfer of genes encoding Vpr, we developed a method to efficiently introduce Vpr protein directly into cells. Vpr packaged into HIV-1 virions lacking a genome induced efficient cell cycle arrest and apoptosis. Introduction of Vpr into tumor cell lines of various tissue origin, including those bearing predisposing mutations in p53, XPA, and hMLH1, induced cell cycle arrest and apoptosis with high efficiency. Significantly, apoptosis mediated by virion-associated Vpr was more effective on rapidly dividing cells compared with slow-growing cells, thus, in concept, providing a potential differential effect between some types of tumor cells and surrounding normal cells. This model system provides a rationale and proof of concept for the development of potential cancer therapeutic agents based on the growth-arresting and apoptotic properties of Vpr.
Stewart
S A
SA
Department of Microbiology, University of California School of Medicine, University of California AIDS Institute, Los Angeles, CA 90095, USA.
Poon
B
B
Jowett
J B
JB
Xie
Y
Y
Chen
I S
IS
D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002461:Cell Line, Transformed; D005434:Flow Cytometry; D016195:G2 Phase / Q000502:physiology; D016336:Gene Products, vpr / Q000235:genetics* / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D015497:HIV-1 / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D016086:Lentivirus / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus