کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5558389 | 1561130 | 2017 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Inactivation of the orphan nuclear receptor NR4A1 contributes to apoptosis induction by fangchinoline in pancreatic cancer cells Inactivation of the orphan nuclear receptor NR4A1 contributes to apoptosis induction by fangchinoline in pancreatic cancer cells](/preview/png/5558389.png)
- Novel anticancer mechanisms of fangchinoline (FCN) were identified.
- FCN is the first natural inactivator of the orphan nuclear receptor NR4A1.
- FCN induces apoptosis, in part, via the NR4A1-dependent proapoptotic pathways.
- FCN represents a natural anticancer agent for treating NR4A1-overexpressing cancer.
Previous studies have demonstrated that the orphan nuclear receptor NR4A1 is overexpressed in human pancreatic cancer and antagonizing this receptor promotes apoptosis and inhibits pancreatic cancer cells and tumor growth. In the present study, we identified fangchinoline, a bisbenzyltetrahydroisoquinoline alkaloid from Stephania tetrandra, as a new inactivator of nuclear NR4A1 and demonstrated that fangchinoline inhibits cell proliferation and induces apoptosis, in part, via the NR4A1-dependent pro-apoptotic pathways in human pancreatic cancer cells. It decreased expression of the antiapoptotic protein survivin by inhibiting Sp1-mediated transcription and induced oxidative stress-mediated endoplasmic reticulum (ER) stress in pancreatic cancer cells. These results suggest that inhibition of NR4A1-mediated transcriptional activity was involved in the anticancer effects of fangchinoline, and fangchinoline represents a novel class of mechanism-based anticancer agents targeting NR4A1 that is overexpressed in pancreatic cancer.
Journal: Toxicology and Applied Pharmacology - Volume 332, 1 October 2017, Pages 32-39