PMID- 36741908
OWN - NLM
STAT- MEDLINE
DCOM- 20230207
LR  - 20230207
IS  - 1875-8630 (Electronic)
IS  - 0278-0240 (Print)
IS  - 0278-0240 (Linking)
VI  - 2023
DP  - 2023
TI  - Tanshinone IIA Inhibits Triple-Negative Breast Cancer Cells MDA-MB-231 via G 
      Protein-Coupled Estrogen Receptor- (GPER-) Dependent Signaling Pathway.
PG  - 8371623
LID - 10.1155/2023/8371623 [doi]
LID - 8371623
AB  - Due to the lack of classic estrogen receptors, there has been a shortage of 
      targeted therapy for triple-negative breast cancer (TNBC), resulting in a poor 
      prognosis. However, the newly discovered G protein-coupled estrogen receptor 
      (GPER) has been found to be expressed in TNBC cells. Salvia miltiorrhiza 
      (Danshen) is an essential Chinese medicine for gynecological disorders, and its 
      component tanshinone IIA (Tan IIA) exerts an anticancer effect. Therefore, this 
      study attempted to investigate whether GPER is involved in the inhibitory effect 
      of Tan IIA on TNBC. We applied various databases and GO pathway analysis to 
      predict the possible mechanism of Tan IIA. We identified 39 overlapping targets, 
      including c-Jun, c-Fos, and caspase-3, and enriched cell cycle-related pathways. 
      Next, we demonstrated the strong binding ability of Tan IIA to GPER by molecular 
      docking assay. In the subsequent validation tests, Cell Counting Kit-8 (CCK8) 
      assay showed that Tan IIA inhibited proliferation of MDA-MB-231 cells time and 
      dose dependently without affecting normal cells. Using Transwell plate, flow 
      cytometry, and Western blot assays, we showed that Tan IIA inhibited migration 
      and induced apoptosis of MDA-MB-231 dose dependently. Importantly, protein 
      expressions of GPER, epidermal growth factor receptor (EGFR), extracellular 
      regulated protein kinases (ERK), c-Fos, and c-Jun were all decreased by Tan IIA 
      dose dependently. Administration of GPER inhibitor partly abolished these 
      effects. Furthermore, nuclear translocation of c-Fos and c-Jun as well as cell 
      cycle-related proteins was downregulated by Tan IIA dose dependently. In summary, 
      Tan IIA could inhibit the proliferation and migration of MDA-MB-231 cells and 
      induce apoptosis, and the possible mechanism may be the regulation of 
      GPER-mediated pathways, suggesting that GPER could be a therapeutic target for 
      TNBC.
CI  - Copyright (c) 2023 Yueshuang He et al.
FAU - He, Yueshuang
AU  - He Y
AUID- ORCID: 0000-0002-7449-0212
AD  - School of Life Sciences, Beijing University of Chinese Medicine, No. 11 East 
      Road, North 3rd Ring Road, Beijing 100029, China.
FAU - Yang, Ke
AU  - Yang K
AD  - School of Chinese Medicine, Beijing University of Chinese Medicine, No. 11 East 
      Road, North 3rd Ring Road, Beijing 100029, China.
FAU - Liu, Jiao
AU  - Liu J
AD  - School of Life Sciences, Beijing University of Chinese Medicine, No. 11 East 
      Road, North 3rd Ring Road, Beijing 100029, China.
FAU - Shi, Danning
AU  - Shi D
AD  - School of Life Sciences, Beijing University of Chinese Medicine, No. 11 East 
      Road, North 3rd Ring Road, Beijing 100029, China.
FAU - Zhang, Zeye
AU  - Zhang Z
AD  - School of Life Sciences, Beijing University of Chinese Medicine, No. 11 East 
      Road, North 3rd Ring Road, Beijing 100029, China.
FAU - Yang, Jiadi
AU  - Yang J
AD  - School of Life Sciences, Beijing University of Chinese Medicine, No. 11 East 
      Road, North 3rd Ring Road, Beijing 100029, China.
FAU - Chen, Meng
AU  - Chen M
AD  - School of Chinese Medicine, Beijing University of Chinese Medicine, No. 11 East 
      Road, North 3rd Ring Road, Beijing 100029, China.
FAU - Zhao, Piwen
AU  - Zhao P
AUID- ORCID: 0000-0001-6993-1135
AD  - School of Life Sciences, Beijing University of Chinese Medicine, No. 11 East 
      Road, North 3rd Ring Road, Beijing 100029, China.
LA  - eng
PT  - Journal Article
DEP - 20230127
PL  - United States
TA  - Dis Markers
JT  - Disease markers
JID - 8604127
RN  - 0 (Receptors, Estrogen)
RN  - 03UUH3J385 (tanshinone)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Humans
MH  - *Receptors, Estrogen/metabolism
MH  - *Triple Negative Breast Neoplasms/drug therapy/metabolism
MH  - Molecular Docking Simulation
MH  - Cell Line, Tumor
MH  - Signal Transduction
MH  - Receptors, G-Protein-Coupled/metabolism
MH  - Apoptosis
MH  - GTP-Binding Proteins/metabolism/pharmacology
MH  - Cell Proliferation
PMC - PMC9897920
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2023/02/07 06:00
MHDA- 2023/02/08 06:00
PMCR- 2023/01/27
CRDT- 2023/02/06 03:37
PHST- 2022/08/15 00:00 [received]
PHST- 2023/01/04 00:00 [revised]
PHST- 2023/01/09 00:00 [accepted]
PHST- 2023/02/06 03:37 [entrez]
PHST- 2023/02/07 06:00 [pubmed]
PHST- 2023/02/08 06:00 [medline]
PHST- 2023/01/27 00:00 [pmc-release]
AID - 10.1155/2023/8371623 [doi]
PST - epublish
SO  - Dis Markers. 2023 Jan 27;2023:8371623. doi: 10.1155/2023/8371623. eCollection 
      2023.