Cytokine and tumor cell apoptosis inducing activity of mda-7/IL-24.

Abstract Melanoma Differentiation Associated gene-7 ( mda-7 )/IL-24 has shown potent tumor cell apoptosis inducing capacity in multiple cancers, making it a strong candidate for use as a human cancer gene therapeutic. Several independent studies have currently documented and confirmed mda-7 /IL-24's cytokine nature including presence of a canonical secretory signal peptide, processing and secretion of the molecule by cells and it's binding to specific interleukin receptors on the cell surface. Receptor binding has been shown to activate the JAK/STAT signal transduction pathway with concomitant stimulation of STAT 1 and 3 transactivators. The physiological role(s) of this molecule in modulating immune responses, as a member of the IL-10 family of cytokines, is not well documented and most current information pertains to its apparently restricted expression patterns in specific cell types with immunomodulatory activity. On the other hand, several additional signal transduction pathways were modulated when cells overexpress mda-7 /IL-24, not all of which are necessarily downstream of mda-7 /IL-24 induced JAK/STAT activation. A summary of the current status of information is presented to provide a perspective for the cytokine-related properties of mda-7 /IL-24 in correlation to its tumor cell apoptosis inducing activity. Moreover, new evidence has surfaced pointing toward apoptosis induction via mechanisms independent of cytokine activity-related JAK/STAT activation.