Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 332, Issue -, Pages 32-39Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2017.07.017
Keywords
NR4A1; Fangchinoline; Pancreatic cancer; Apoptosis; Sp1; ER stress
Categories
Funding
- National Research Foundation of Korea [NRF-2014R1A1A2059385]
- Cooperative Research Program for Agriculture Science and Technology Development, Rural Development Administration, Republic of Korea [PJ012284012017]
- Rural Development Administration, Republic of Korea
- Rural Development Administration (RDA), Republic of Korea [PJ012284012017] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
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. (C) 2017 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available