Department of Food Science and Technology, Keimyung University, Daegu 42601, Korea.
National Institute for Korean Medicine Development, Gyeongsan 38540, Korea.
Molecules. 2021 Apr 16;26(8):2316. doi: 10.3390/molecules26082316.
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.
孤儿核受体 4A1（NR4A1）在胰腺癌中过表达，并表现出致癌活性，NR4A1 的沉默和其失活剂的治疗已被证明能抑制胰腺癌细胞和肿瘤生长。在这项研究中，我们鉴定出蔺草酚 A（BCA）是一种新的 NR4A1 抑制剂，并表明 BCA 通过诱导人胰腺癌细胞中 NR4A1 介导的凋亡途径部分抑制细胞生长。BCA 下调特异性蛋白 1（Sp1）介导的抗凋亡蛋白生存素的表达，并激活内质网（ER）应激介导的凋亡途径。这些结果表明，NR4A1 的失活有助于 BCA 的抗癌作用，并且 BCA 代表了一种针对许多类型人类癌症中过表达的 NR4A1 的潜在抗癌剂。
