PMID- 32435622
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 10
DP  - 2020
TI  - Caffeic Acid Phenethyl Ester Prevents Colitis-Associated Cancer by Inhibiting 
      NLRP3 Inflammasome.
PG  - 721
LID - 10.3389/fonc.2020.00721 [doi]
LID - 721
AB  - Long-lasting inflammation in the intestinal tract renders individuals susceptible 
      to colitis-associated cancer (CAC). The NOD-like receptor protein 3 (NLRP3) 
      inflammasome plays a key role in the progression of inflammatory bowel disease 
      and CAC. Therefore, identifying effective drugs that prevent CAC by targeting 
      NLRP3 inflammasome is of great interest. Here, we aimed to evaluate the 
      anti-inflammatory effect of caffeic acid phenethyl ester (CAPE) on bone 
      marrow-derived macrophages (BMDMs), THP-1 cells, and azoxymethane/dextran sulfate 
      sodium (AOM/DSS)-induced colon cancer mouse model. We also investigated the 
      anti-tumor mechanism of CAPE. We found that CAPE decreased NLRP3 inflammasome 
      activation in BMDMs and THP-1 cells and protected mice from colorectal cancer 
      induced by AOM/DSS. CAPE regulated NLRP3 at the post-transcriptional level by 
      inhibiting reactive oxygen species (ROS) production. However, CAPE did not affect 
      NLRP3 or IL-1beta transcription, but instead enhanced NLRP3 binding to ubiquitin 
      molecules, promoting NLRP3 ubiquitination, and contributing to the anti-tumor 
      effect in the AOM/DSS mouse model. Moreover, CAPE suppressed the interaction 
      between NLRP3 and CSN5 but enhanced that between NLRP3 and Cullin1 both in vivo 
      and in vitro. Altogether, our findings demonstrate that CAPE prevents CAC by 
      post-transcriptionally inhibiting NLRP3 inflammasome. Thus, CAPE may be an 
      effective candidate for reducing the risk of CAC in patients with inflammatory 
      bowel disease.
CI  - Copyright (c) 2020 Dai, Jiang, Sun, Liu, Meng, Ding, Jing and Ju.
FAU - Dai, Guoliang
AU  - Dai G
AD  - Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of 
      Chinese Medicine, Nanjing, China.
FAU - Jiang, Zhitao
AU  - Jiang Z
AD  - Department of Pharmacy, Zhangjiagang Hospital of Traditional Chinese Medicine 
      Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, China.
FAU - Sun, Bingting
AU  - Sun B
AD  - Department of Pharmacy, Nanjing Hospital of Chinese Medicine Affiliated to 
      Nanjing University of Chinese Medicine, Nanjing, China.
FAU - Liu, Chao
AU  - Liu C
AD  - Department of Pharmacy, Nanjing First Hospital, Nanjing Medical University, 
      Nanjing, China.
FAU - Meng, Qinghai
AU  - Meng Q
AD  - School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
FAU - Ding, Kang
AU  - Ding K
AD  - National Center of Colorectal Surgery, Jiangsu Integrate Colorectal Oncology 
      Center, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of 
      Chinese Medicine, Nanjing, China.
FAU - Jing, Wen
AU  - Jing W
AD  - Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of 
      Chinese Medicine, Nanjing, China.
FAU - Ju, Wenzheng
AU  - Ju W
AD  - Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of 
      Chinese Medicine, Nanjing, China.
LA  - eng
PT  - Journal Article
DEP - 20200506
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC7218129
OTO - NOTNLM
OT  - BMDMs
OT  - IL-1beta
OT  - NLRP3
OT  - THP-1 cells
OT  - caffeic acid phenethyl ester
OT  - colitis-associated cancer
EDAT- 2020/05/22 06:00
MHDA- 2020/05/22 06:01
PMCR- 2020/01/01
CRDT- 2020/05/22 06:00
PHST- 2020/01/05 00:00 [received]
PHST- 2020/04/16 00:00 [accepted]
PHST- 2020/05/22 06:00 [entrez]
PHST- 2020/05/22 06:00 [pubmed]
PHST- 2020/05/22 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2020.00721 [doi]
PST - epublish
SO  - Front Oncol. 2020 May 6;10:721. doi: 10.3389/fonc.2020.00721. eCollection 2020.