Embelin inhibits pancreatic cancer progression by directly inducing cancer cell apoptosis and indirectly restricting IL-6 associated inflammatory and immune suppressive cells1

•Embelin inhibits pancreatic cancer cells proliferation and migration in vitro.•Embelin promotes the apoptosis of pancreatic cancer cells in vitro.•Embelin suppresses pancreatic cancer progression in vivo.•Embelin restricts IL-6 associated inflammatory and immune suppressive cells.•Embelin promotes p53 and suppresses STAT3 signaling in pancreatic cancer.

Pancreatic cancer is an aggressive malignancy and unresponsive to conventional chemotherapies. Here, the anti-inflammatory and anti-tumor effects of embelin on pancreatic cancer were investigated. Embelin significantly attenuated cells invasion, proliferation and induced apoptosis through inhibition of STAT3 and activation of p53 signaling pathways. Embelin substantially reduced the tumorigenicity of pancreatic cancer cells in vivo, which was associated with reduced inflammatory cells and immune suppressive cells, IL-17A+ Th17, GM-CSF+ Th, MDSCs and Treg, through inhibition of IL-6 secretion. Moreover, embelin decrease IL-6-induced STAT3 phosphorylation. In summary, embelin represents a novel therapeutic drug candidate for the clinical treatment of pancreatic cancer.