Apoptotic signal pathways and regulatory mechanisms of cancer cells induced by IL-24

The melanoma differentiation-associated gene-7(mda-7), IL-24, has the specific functions that induce cancer cell apoptosis without doing harm to normal cells. We systematically review the apoptotic signal pathways and their regulatory mechanisms induced by Ad.IL-24 and IL-24 in diverse cancer cells. IL-24 can participate in varied signal transduction pathways, including JAK, p38 MAPK, Wnt/β-catenin, JNK, ER stress and mitochondria-associated signal pathways. And we review five proteins interacting with IL-24, including Bip/GRP78, S1R, PKR, Beclin1 and soluble clusterin, which are relative to the tumor-specific effect of IL-24. It is speculated that ER stress, G-protein pathways and MAPK signal pathways may be the primary upstream effectors which activate the sequential downstream mediators resulting in apoptosis induced by IL-24 in tumor cells. Experimental results also show that IL-24 sensitizes cancer cells and indirectly promotes apoptosis rather than functions as a direct apoptosis inducer itself.