Reversing translational suppression and induction of toxicity in pancreatic cancer cells using a chemoprevention gene therapy approach.

摘要: Pancreatic cancer is an aggressive disease with limited therapeutic options. Melanoma differentiation–associated gene-7/interleukin-24 (mda-7/IL-24), a potent antitumor cytokine, shows cancer-specific toxicity in vast array of human cancers, inducing endoplasmic reticulum stress and apoptosis, toxic autophagy, immune response, antiangiogenic effect, significant “bystander” anticancer effect that leads to enhanced production this cytokine through autocrine paracrine loops. Unfortunately, mda-7/IL-24 application pancreatic has been restricted because “translational block” occurring after Ad.5-mda-7 gene delivery. Our previous research focused on developing approaches overcome block increase the translation MDA-7/IL-24 protein, thereby promoting its subsequent effects cells. We demonstrated reactive oxygen species (ROS) adenoviral infection greater into protein results In study we demonstrate novel chimeric serotype adenovirus, Ad.5/3-mda-7, displays efficacy delivering compared Ad.5-mda-7, although overall still remains low. additionally show d-limonene, dietary monoterpene known induce ROS, capable overcoming translational when used combination This increased polysome association mRNA, activation preinitiation complex machinery cells, culminates mda-7/IL-24–mediated toxicity.