PROSPECTIVE ROLES OF IL-24 IN THE TUMORIGENESIS AND DEVELOPMENT OF CANCERS

Abstract

Interleukin-24 (IL-24)/melanoma differentiation-associated gene-7 (mda-7), a novel tumor suppressor/cytokine, exerts tumor-selective inhibition of cells growth, induction of apoptosis, and suppression of angiogenesis in a broad spectrum of cancer cell types without harming the equivalent normal cells. Moreover, the low transcript levels and protein expression of IL-24 have been found to be significantly associated with unfavorable pathological phenotypes in breast cancer tissues. Furthermore, the ectopic expression of IL-24 in cancer cells via transfection with a plasmid comprising IL-24 cDNA or via administration of IL-24 containing recombinant adenovirus (Ad.IL-24) can effectively inhibit the growth and induce apoptosis in a wide array of cancer cells and rodent tumors both in vitro and in vivo. However, overexpression of IL-24 in normal primary cells does not elicit any effect on its growth and viability, indicating that IL-24 can act as a crucial target and therapeutic gene for cancer gene therapy. Mechanistically, the binding of IL-24 cytokine with its receptor pair in different tumor cells activates the JAK-STAT signal transduction pathway, serine/threonine-protein kinase (PKR) pathway, mitochondrial apoptosis signaling pathway, and inhibits CD31/PECAM pathway to inhibit cancer cell growth, induce apoptosis and regulate tumor vascularization. Herein, we reviewed the research progress on biochemical characteristics of IL-24 and its selective role in carcinogenesis, to provide a detailed understanding of the functional mechanism of IL-24. Overall, this study presented IL-24 as a potent antitumor drug target for the development of a more accurate therapeutic strategy and cancer gene therapy.