Lentiviral delivery of HIV-1 Vpr protein induces apoptosis in transformed cells

Most current anticancer therapies act by inducing tumor cell stasis followe d by apoptosis. HIV-1 Vpr effectively induces apoptosis of T cells after ar rest of cells at a G(2)/M checkpoint. Here, we investigated whether this pr operty of Vpr could be exploited for use as a potential anticancer agent. A s a potentially safer alternative to transfer of genes encoding Vpr, we dev eloped a method to efficiently introduce Vpr protein directly into cells. V pr packaged into HIV-1 Virions lacking a genome induced efficient cell cycl e arrest and apoptosis. Introduction of Vpr into tumor cell lines of variou s 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 effecti ve on rapidly dividing cells compared with slow-growing cells, thus, in con cept, 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 a gents based on the growth-arresting and apoptotic: properties of Vpr.