PMID- 33622869
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20211204
IS  - 1791-7549 (Electronic)
IS  - 0258-851X (Print)
IS  - 0258-851X (Linking)
VI  - 35
IP  - 2
DP  - 2021 Mar-Apr
TI  - Drug Screening of Potential Multiple Target Inhibitors for Estrogen 
      Receptor-alpha-positive Breast Cancer.
PG  - 761-777
LID - 10.21873/invivo.12317 [doi]
AB  - BACKGROUND/AIM: Estrogen receptor alpha (ERalpha) antagonist is the most common treatment 
      for ERalpha-positive breast cancer. However, compensatory signaling contributes to 
      resistance to ERalpha antagonists. Thus, to explore the potential agents for 
      targeting compensatory signaling, we screened multiple target inhibitors for 
      breast cancer treatment. MATERIALS AND METHODS: We attempted to build a 
      structure-based virtual screening model that can find potential compounds and 
      assay the anticancer ability of these drugs by overall cell survival assay. The 
      downstream compensatory phosphorylated signaling was measured by immunoblotting. 
      RESULTS: Hamamelitannin and glucocheirolin were hits for ERalpha, phosphoinositide 
      3-kinase (PI3K), and KRAS proto-oncogene, GTPase (KRAS), which were active 
      against estrogen and epidermal growth factor-triggered proliferation. 
      Additionally, we select aminopterin as a hit for ERalpha, PI3K, KRAS, and SRC 
      proto-oncogene, non-receptor tyrosine kinase (SRC) with inhibitory activities 
      toward AKT serine/threonine kinase 1 (AKT) and mitogen-activated protein kinase 
      kinase (MEK) signaling. CONCLUSION: Our structure-based virtual screening model 
      selected hamamelitannin, glucocheirolin, aminopterin, and pemetrexed as compounds 
      that may act as potential inhibitors for improving endocrine therapies for breast 
      cancer.
CI  - Copyright(c) 2021, International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Dai, Yun-Hao
AU  - Dai YH
AD  - School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
AD  - Chinese Medicine Research and Development Center, Center for Molecular Medicine, 
      China Medical University Hospital, China Medical University, Taichung, Taiwan, 
      R.O.C.
FAU - Chen, Guan-Yu
AU  - Chen GY
AD  - Chinese Medicine Research and Development Center, Center for Molecular Medicine, 
      China Medical University Hospital, China Medical University, Taichung, Taiwan, 
      R.O.C.
FAU - Tang, Chih-Hsin
AU  - Tang CH
AD  - Department of Pharmacology, School of Medicine, China Medical University, 
      Taichung, Taiwan, R.O.C.
AD  - Chinese Medicine Research Center, Drug Development Center, China Medical 
      University, Taichung, Taiwan, R.O.C.
AD  - Department of Biotechnology, College of Medical and Health Science, Asia 
      University, Taichung, Taiwan, R.O.C.
FAU - Huang, Wei-Chien
AU  - Huang WC
AD  - Chinese Medicine Research and Development Center, Center for Molecular Medicine, 
      China Medical University Hospital, China Medical University, Taichung, Taiwan, 
      R.O.C.
AD  - Chinese Medicine Research Center, Drug Development Center, China Medical 
      University, Taichung, Taiwan, R.O.C.
AD  - Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 
      Taiwan, R.O.C.
AD  - The Biotechnology Department, College of Medical and Health Science, Asia 
      University, Taichung, Taiwan, R.O.C.
FAU - Yang, Juan-Cheng
AU  - Yang JC
AD  - Chinese Medicine Research and Development Center, Center for Molecular Medicine, 
      China Medical University Hospital, China Medical University, Taichung, Taiwan, 
      R.O.C.; yachwu@mail.cmu.edu.tw qq9113054@gmail.com.
FAU - Wu, Yang-Chang
AU  - Wu YC
AD  - Chinese Medicine Research and Development Center, Center for Molecular Medicine, 
      China Medical University Hospital, China Medical University, Taichung, Taiwan, 
      R.O.C.; yachwu@mail.cmu.edu.tw qq9113054@gmail.com.
AD  - The Biotechnology Department, College of Medical and Health Science, Asia 
      University, Taichung, Taiwan, R.O.C.
AD  - Graduate Institute of Integrated Medicine, College of Chinese Medicine, China 
      Medical University, Taichung, Taiwan, R.O.C.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - In Vivo
JT  - In vivo (Athens, Greece)
JID - 8806809
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Receptors, Estrogen)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - *Breast Neoplasms/drug therapy/genetics
MH  - Cell Line, Tumor
MH  - Drug Evaluation, Preclinical
MH  - Early Detection of Cancer
MH  - Estrogen Receptor alpha/genetics
MH  - Female
MH  - Humans
MH  - Phosphatidylinositol 3-Kinases
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins c-akt
MH  - Receptors, Estrogen
PMC - PMC8045062
OTO - NOTNLM
OT  - ER+ breast cancer
OT  - Multiple inhibitors
OT  - aminopterin
COIS- The Authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as no conflict of 
      interest.
EDAT- 2021/02/25 06:00
MHDA- 2021/06/22 06:00
PMCR- 2021/03/03
CRDT- 2021/02/24 05:37
PHST- 2020/10/21 00:00 [received]
PHST- 2020/11/21 00:00 [revised]
PHST- 2020/11/24 00:00 [accepted]
PHST- 2021/02/24 05:37 [entrez]
PHST- 2021/02/25 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2021/03/03 00:00 [pmc-release]
AID - 35/2/761 [pii]
AID - 10.21873/invivo.12317 [doi]
PST - ppublish
SO  - In Vivo. 2021 Mar-Apr;35(2):761-777. doi: 10.21873/invivo.12317.