Abstract 3831: Sodium butyrate induces differential expression of Th17 and inflammatory cytokines during apoptosis in human U937 leukemia cells

Abstract

Abstract Sodium butyrate (NaB) is a sodium salt of butyric acid. It is a strong HDAC1 inhibitor, which has been implicated in many studies as a potential therapy for various forms of cancer including prostate cancer. Also, it has been suggested as a potential therapy for hemoglobin disorders including sickle cell diseases and leukemia because of its ability to promote both total globin and gamma globin synthesis during erythroid differentiation. Previously NaB has been shown to active apoptosis in several cancer cell lines including U937 and K562 leukemia cell lines. However, it is not known whether it has the capability to modulate cytokines expression in cancer cells and alter the cancer microenvironment, which was the purpose of this study. We exposed U937 leukemia cells to NaB at 5 mM or 10 mM for 24 or 48 hours, conditions under which NaB is known to induce apoptosis in these cells. The culture media of the cells were harvested and analyzed by Human Multi-Analyte Cytokine ELISArray method and by protein/antibody cytokine arrays for levels of TH17-type and Inflammatory cytokines. We also monitored cells for caspase 3 activation and cell viability as evidence of apoptosis. Our results indicate that NaB induces differential expression of several TH17-type and Inflammatory cytokines from 2 to 10-fold within 24 hours. The ranking order of induction of TH17-type cytokines by NaB was IL-17A>IL-5>IL-4>G-CSF>IL-10>TNF>IL-12>IFNγ while induction of inflammatory cytokines was of the ranking order: IL-1A>IL-8>IL-10. Also within 24 hours, NaB treatment caused at least 2-fold activation of caspase 3 and reduced the cell viability by 60 %. These observations indicate that NaB induces differential expression of both TH17 and Inflammatory cytokines during induction of apoptosis. The data also suggest that while promoting cancer cell death by apoptosis, NaB also has the potential to influence cancer microenvironment by inducing differential expression and secretion of cytokines. Such an effect could influence the biology of both the normal and cancer cells and could alter the status of the patient who is receiving NaB therapy. Further studies are in progress to determine whether NaB has similar effects in human monocytes. Supported by NCI U54 cancer grants # 5 U54 CA091408-09. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3831.