Stress-associated hormone, norepinephrine, increases proliferation and IL-6 levels of human pancreatic duct epithelial cells and can be inhibited by the dietary agent, sulforaphane

Abstract

In current literature there is evidence that psychological factors can affect the incidence and progression of some cancers. Data obtained from animal models support the hypothesis that stress can be a cofactor. The underlying mechanisms for the association between psychological factors and pancreatic cancer are very poorly understood. In this study, we examined the possible growth promoting effects of the stress-associated hormone, norepinephrine, on immortalized human pancreatic duct epithelial cells. Our results suggest that norepinephrine can increase cell proliferation of human pancreatic duct epithelial cells. We also evaluated the ability of norepinephrine to induce interleukin-6 (IL-6), interleukin-10 (IL-10), and vascular endothelial growth factor (VEGF). All of which may promote oncogenesis of immortalized human pancreatic duct epithelial cells. We found that norepinephrine can increase the IL-6 and VEGF but not IL-10 levels secreted by human pancreatic duct epithelial cells. Since norepinephrine can increase cell proliferation of human pancreatic duct epithelial cells, we performed further testing to see if dietary agents, sulforaphane and resveratrol, can inhibit norepinephrine-mediated increases in cell proliferation in human pancreatic duct epithelial cells. Interestingly, our results demonstrated that sulforaphane but not resveratrol inhibits norepinephrine-mediated increases in cell viability in human pancreatic duct epithelial cells. Furthermore, sulforaphane also inhibits norepinephrine-mediated increase of the IL-6 levels but not VEGF levels. Our study is the first to demonstrate that stress-associated hormone, norepinephrine, can increase the cell proliferation and IL-6 levels of human pancreatic duct epithelial cells, which can be inhibited by sulforaphane, a chemopreventive agent and a natural compound from the Cruciferous vegetables.