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

abstract

• 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 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 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.

authors

• Safe, Stephen

published proceedings

• Molecules

author list (cited authors)

• Lee, H., Kim, S., Kim, B., Safe, S., & Lee, S.

citation count

• 4

complete list of authors

• Lee, Hyo-Seon||Kim, Soo-Hyun||Kim, Bo-Mi||Safe, Stephen||Lee, Syng-Ook

publication date

• January 2021

publisher

• MDPI  Publisher

published in

• Molecules  Journal

keywords

• Animals
• Antineoplastic Agents
• Apoptosis
• Broussochalcone A
• Cell Line, Tumor
• Chalcones
• Endoplasmic Reticulum Stress
• Er Stress
• Humans
• Nr4a1
• Nuclear Receptor Subfamily 4, Group A, Member 1
• Pancreatic Cancer
• Pancreatic Neoplasms
• Reactive Oxygen Species
• Resorcinols
• Sp1

PubMed Central ID

• 33923503

Digital Object Identifier (DOI)

• 10.3390/molecules26082316

start page

• 2316

end page

• 2316

volume

• 26

issue

• 8

URL

• http://dx.doi.org/10.3390/molecules26082316