The objective of this study was to determine the effect of macrophages on growth of human colon cancer cells. The results showed that co-culture of colon cancer cells with macrophages inhibited the growth of colon cancer cells (HCT116 and SW620) depending on the number of macrophages, RAW 264.7 cells, and activated THP-1 cells accompanied by down regulation of pSTAT3 in cancer cells. We also found that expression and release of cancer cell growth inhibitory cytokines, IL-1 receptor antagonist (IL-1ra) and IL-10, was increased in macrophages. Blocking of the STAT3 pathway with specific inhibitor and siRNA of STAT3 abolished the growth of colon cancer cells and expression of IL-1ra and IL-10. In addition, neutralization of IL-1ra and IL-10 with antibodies resulted in reversal of macrophage-induced inhibition of cancer cell growth. These data showed that IL-1ra and IL-10 released from macrophages inhibit growth of colon cancer cells through inhibition of the STAT3 pathway.
Background : Tooth vitality is reflected by the health of dental pulp. Schisandrin C is a natural compound extracted from the fruit of Schisandra chinensis which has anti-inflammatory and anti-oxidant properties. The role of Schisandrin C on human dental pulp cells (HDPCs) has not been studied yet. This study examined the properties of Schisandrin C as an anti-inflammatory and anti-oxidant compound, and whether its characteristics promote mitochondrial biogenesis in HDPCs. Methods and Results : HDPCs were extracted from fresh third molars and cultured. Reactive oxidative stress (ROS) and nitric oxide (NO) formation were analyzed by a Muse cell analyzer. Western blotting and gelatin zymography were used to identify the presence of anti-oxidants, as well as inflammatory and mitochondrial biogenesis. Confocal microscopy was used for the detection of mitochondrial activity. Schisandrin C inhibited lipopolysaccharide (LPS)-stimulated inflammatory molecules; intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), matrix metalloproteinase-2 and -9 (MMP-2/9), NO production, ROS formation and the mitogen-activated protein (MAPK) pathway through minimizing the nuclear factor kappa B (NF-kB) translocation. Schisandrin C increased the expression of superoxide dismutase (SOD) enzymes as well as heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) through the phosphorylated-protein kinase B (p-AKT) and nuclear factor erythroid 2-related factor-2 (Nrf-2) pathways. The anti-inflammatory and anti-oxidant properties of Schisandrin C promoted mitochondrial biogenesis. Conclusions : These results suggest that Schisandrin C may be used as an anti-inflammatory compound to reduce oral inflammation such as pulpitis.