Broussochalcone A Is a Novel Inhibitor of the Orphan Nuclear Receptor NR4A1 and Induces Apoptosis in Pancreatic Cancer Cells

Broussochalcone A Is a Novel Inhibitor of the Orphan Nuclear Receptor NR4A1 and Induces Apoptosis in Pancreatic Cancer Cells

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The orphan nuclear receptor 4A1 (NR4A1) is overexpressed in pancreatic cancer and exhibits pro-oncogenic activity, and NR4A1 silencing and treatment with its inactivators has been shown to inhibit pancreatic cancer cells and tumor growth.In this study, we identified broussochalcone A (BCA) as a new NR4A1 inhibitor and demonstrated that BCA inhibits reebok classic grün cell growth partly by inducing NR4A1-mediated apoptotic pathways in human pancreatic cancer cells.BCA downregulated specificity protein 1 (Sp1)-mediated expression of an anti-apoptotic protein, survivin, and activated the endoplasmic reticulum (ER) stress-mediated apoptotic venus tops and blouses pathway.These results suggest that NR4A1 inactivation contributes to the anticancer effects of BCA, and that BCA represents a potential anticancer agent targeting NR4A1 that is overexpressed in many types of human cancers.