IFN-γ Induces Apoptosis in HL-60 Cells Through Decreased Bcl-2 and Increased Bak Expression

ABSTRACT Interferons (IFNs) are pleiotropic cytokines responsible for inducing innate and adaptive immunities against a wide range of viruses and other microbial pathogens. In addition, IFNs also exert antitumor activities due to their antiproliferative, immunomodulatory, proapoptotic functions. In the last decades, the successful clinical application of IFNs for treatment of cancer, particularly leukemia, has improved the quality and longevity of life for many patients. The induction of tumor cell apoptosis by IFNs is believed to contribute, at least in part, to the beneficial effects. IFN subtypes, such as IFN-α, IFN-β, and IFN-γ, induce apoptosis through cell type-specific signaling pathways, and several putative IFN-stimulated genes (ISGs) with proapoptotic functions have been identified. Here, we analyzed the ability of IFN-α, IFN-β, or IFN-γ to induce apoptosis in several malignant hematologic cell lines. We found that treatment with IFN-γ, but not IFN-α, or IFN-β, specifically induces HL-60 leukemi...