AI Article Synopsis
- The orphan nuclear receptor 4A1 (NR4A1) is found to be overexpressed in pancreatic cancer, promoting tumor growth, and its silencing or inactivation can slow down cancer cell proliferation.
- Broussochalcone A (BCA) has been identified as a new inhibitor of NR4A1, which helps suppress cell growth by triggering apoptotic pathways in pancreatic cancer cells.
- BCA reduces levels of the anti-apoptotic protein survivin and activates stress-induced apoptosis, suggesting that NR4A1 inactivation plays a key role in BCA's potential as an anticancer treatment targeting various cancers.
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073833 | PMC |
| http://dx.doi.org/10.3390/molecules26082316 | DOI Listing |
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