Recombinant Human IL-24 Suppresses Lung Carcinoma Cell Growth via Induction of Cell Apoptosis and Inhibition of Tumor Angiogenesis

Abstract

Previous studies have shown that interleukin-24 (IL-24; mda-7) as a novel tumor suppressor gene has tumor-suppressive activity against a broad spectrum of human cancers. However, the therapeutic effect of the recombinant human IL-24 (rhIL-24) protein purified from prokaryotic cells on human lung cancers has not been reported. In this study, we cloned the human gene coding for IL-24 from lipopolysaccharide-activated human peripheral blood mononuclear cells (PBMCs) by reverse-transcriptase polymerase chain reaction and constructed an expression vector pBV220-IL-24. We then transfected Escherichia coli DH5alpha with pBV220-IL-24. The soluble rhIL-24 was obtained from purified insoluble inclusion bodies of transfected cells by a denaturing and renaturing process. We demonstrated that the purified soluble rhIL-24 protein with 18.5 kappaDa was capable of (1) inducing in vitro apoptosis of A549 lung carcinoma cells; (2) activating PBMCs to secrete cytokines such as IL-6, tumor necrosis factor-alpha, and interferon-gamma; (3) inhibiting the formation of blood capillaries on chicken embryonic allantois and in vivo tumor angiogenesis; and (4) inhibiting A549 lung tumor cell growth in vitro and in vivo. Therefore, our results indicate its potent suppressive effect on human lung carcinoma cell line and warrant its further investigation for therapeutic application against human lung cancer.