Interferon beta lipofection II. Mechanisms involved in cell death and bystander effect induced by cationic lipid mediated interferon-beta gene transfer to human tumor cells

VILLAVERDE M. S.; M. L. GIL-CARDEZA; G. C. GLIKIN; L. M. E. FINNOCHIARO

CANCER GENE THERAPY

NATURE PUBLISHING GROUP

Año: 2012 vol. 19 p. 420 - 430

0929-1903

ABSTRACT We evaluated the cytotoxic effects (apoptosis, necrosis and early senescence) of human interferon-â (hIFNâ) gene lipofection. The cytotoxicity of hIFNâ gene lipofection resulted equivalent to that of the corresponding addition of the recombinant protein (rhIFNâ) on human tumor cell lines derived from Ewing?s sarcoma (EW7 and COH) and colon (HT-29) carcinomas. However, it was stronger than rhIFNâ on melanoma (M8), and breast adenocarcinoma (MCF7). To reveal the mechanisms involved in these differences, we compared the effects of hIFNâ gene and hrIFNâ protein on EW7 and M8 (sensitive and resistant to hrIFNâ protein, respectively). Lipofection with hIFNâ gene caused a mitochondrial potential decrease simultaneous with an increase of oxidative stress in both cell lines. However, rhIFNâ protein displayed the same pattern of response only in EW7 sensitive cell line. The great bystander effect of the hIFNâ gene lipofection, involving the production of reactive oxygen species, would be among the main causes of its success. In EW7, this effect killed more than 60% of EW7 cell population, even though only 1% of cells were expressing the transgene. Since hIFNâ gene was effective even in the rhIFNâ protein resistant M8 cell line and in a way not limited by low lipofection efficiency, these results strongly support the clinical potential of this approach.