PMID- 32492489
OWN - NLM
STAT- MEDLINE
DCOM- 20210706
LR  - 20210706
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 159
DP  - 2020 Sep
TI  - Oroxylin A suppresses ACTN1 expression to inactivate cancer-associated 
      fibroblasts and restrain breast cancer metastasis.
PG  - 104981
LID - S1043-6618(20)31289-5 [pii]
LID - 10.1016/j.phrs.2020.104981 [doi]
AB  - Tumor initiation and progression are not only ascribed to the behavior of cancer 
      cells, but also profoundly influenced by the tumor microenvironment. Inside, 
      cancer-associated fibroblasts (CAFs) have become key factors to accelerate growth 
      and metastasis for the abundance in most solid tumors. Our group previously 
      reported that Oroxylin A (OA), a flavone from Scutellaria Baicalensis Georgi, 
      possess the ability to suppress growth and invasion of several tumor cells. 
      However, the regulatory effect of OA on stromal microenvironment is poorly 
      understood. In this study, breast cancer-induced fibroblasts and primary breast 
      CAFs from MMTV-PyMT mice were used to evaluate the influence of OA on the 
      activation of fibroblasts. Results showed that OA could decrease the expression 
      of alpha-SMA, fibronectin, vimentin and matrix metalloproteinases (MMPs). Thus, 
      OA-deactivated CAFs did not further promote the proliferation and invasion in 
      breast cancer cells. In vivo experiments, OA could also impede tumor metastasis 
      through exhausting progressive CAFs. Mechanically, OA could specifically bind 
      ACTN1 and significantly inhibit its expression to prevent CAF activation. As a 
      consequence, OA could decrease the phosphorylation of FAK and STAT3, and reduce 
      the secretion of CCL2 in CAFs. Altogether, OA could remodel stromal 
      microenvironment and it is a potential therapeutic agent in breast cancer.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Cao, Yue
AU  - Cao Y
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, 
      China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's 
      Republic of China.
FAU - Cao, Wangjia
AU  - Cao W
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, 
      China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's 
      Republic of China.
FAU - Qiu, Yangmin
AU  - Qiu Y
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, 
      China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's 
      Republic of China.
FAU - Zhou, Yuxin
AU  - Zhou Y
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, 
      China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's 
      Republic of China.
FAU - Guo, Qinglong
AU  - Guo Q
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, 
      China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's 
      Republic of China.
FAU - Gao, Yuan
AU  - Gao Y
AD  - Pharmaceutical Animal Experimental Center, School of Basic Medicine and Clinical 
      Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, 
      People's Republic of China. Electronic address: cpugaoyuan@163.com.
FAU - Lu, Na
AU  - Lu N
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, 
      China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's 
      Republic of China. Electronic address: nalu@cpu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200531
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Actn1 protein, mouse)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Flavonoids)
RN  - 11003-00-2 (Actinin)
RN  - 53K24Z586G (5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one)
SB  - IM
MH  - Actinin/genetics/*metabolism
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/metabolism/*pharmacology
MH  - Breast Neoplasms/*drug therapy/genetics/metabolism/pathology
MH  - Cancer-Associated Fibroblasts/*drug effects/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/*drug effects
MH  - Down-Regulation
MH  - Female
MH  - Flavonoids/metabolism/*pharmacology
MH  - Gene Expression Regulation, Neoplastic
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Mice, Transgenic
MH  - Neoplasm Metastasis
MH  - Phenotype
MH  - Protein Binding
MH  - Signal Transduction
MH  - Tumor Microenvironment
OTO - NOTNLM
OT  - ACTN1
OT  - CAFs
OT  - Cancer metastasis
OT  - OA
OT  - Oroxylin A (CID: 5320315)
OT  - STAT3
EDAT- 2020/06/04 06:00
MHDA- 2021/07/07 06:00
CRDT- 2020/06/04 06:00
PHST- 2020/01/22 00:00 [received]
PHST- 2020/04/24 00:00 [revised]
PHST- 2020/05/26 00:00 [accepted]
PHST- 2020/06/04 06:00 [pubmed]
PHST- 2021/07/07 06:00 [medline]
PHST- 2020/06/04 06:00 [entrez]
AID - S1043-6618(20)31289-5 [pii]
AID - 10.1016/j.phrs.2020.104981 [doi]
PST - ppublish
SO  - Pharmacol Res. 2020 Sep;159:104981. doi: 10.1016/j.phrs.2020.104981. Epub 2020 
      May 31.