PMID- 33393692
OWN - NLM
STAT- MEDLINE
DCOM- 20210727
LR  - 20210727
IS  - 1099-0461 (Electronic)
IS  - 1095-6670 (Linking)
VI  - 35
IP  - 4
DP  - 2021 Apr
TI  - N-arachidonoyl dopamine inhibits epithelial-mesenchymal transition of breast 
      cancer cells through ERK signaling and decreasing the cellular cholesterol.
PG  - e22693
LID - 10.1002/jbt.22693 [doi]
AB  - N-acyl dopamines (NADAs) are bioactive lipids of the endovanilloid family with 
      known cytotoxicity for the cancer cells; however, the available data on the 
      participation of the endovanilloids in epithelial-mesenchymal transition (EMT) 
      and cancer stemness are controversial. This study unveils the inhibitory role of 
      N-arachidonoyl dopamine (AA-DA), a typical representative of the NADA family, in 
      breast cancer cell migration, EMT, and stemness. AA-DA treatment also led to a 
      decrease in cholesterol biosynthesis gene expressions, and addition of exogenous 
      cholesterol reverted these AA-DA-mediated inhibitory effects. Notably, AA-DA 
      treatment inhibited the key regulatory gene of the cholesterol biosynthesis 
      pathway, sterol regulatory element-binding protein 1 (SREBP1), with concurrent 
      repression of the endoplasmic reticulum kinase 1/2 (ERK1/2) pathway. Furthermore, 
      U0126, an ERK inhibitor, inhibited SREBP1 and decreased cellular cholesterol 
      level, unwinding the molecular mechanism behind AA-DA-mediated anticancer 
      activity. Thus, we, for the first time, revealed that AA-DA counteracts breast 
      cancer EMT via inhibition of ERK signaling and cholesterol content.
CI  - (c) 2021 Wiley Periodicals LLC.
FAU - Bandyopadhayaya, Shreetama
AU  - Bandyopadhayaya S
AD  - Department of Biochemistry, School of Life Sciences, Central University of 
      Rajasthan, Ajmer, Rajasthan, India.
FAU - Akimov, Mikhail G
AU  - Akimov MG
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia.
FAU - Verma, Ranjeet
AU  - Verma R
AD  - Department of Biochemistry, School of Life Sciences, Central University of 
      Rajasthan, Ajmer, Rajasthan, India.
FAU - Sharma, Ankit
AU  - Sharma A
AD  - Department of Biochemistry, School of Life Sciences, Central University of 
      Rajasthan, Ajmer, Rajasthan, India.
FAU - Sharma, Divya
AU  - Sharma D
AD  - Department of Biochemistry, School of Life Sciences, Central University of 
      Rajasthan, Ajmer, Rajasthan, India.
FAU - Kundu, Gopal C
AU  - Kundu GC
AD  - School of Biotechnology, Institute of Eminence, KIIT Deemed to be University, 
      Bhubaneswar, India.
FAU - Gretskaya, Natalia M
AU  - Gretskaya NM
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia.
FAU - Bezuglov, Vladimir V
AU  - Bezuglov VV
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia.
FAU - Mandal, Chandi C
AU  - Mandal CC
AUID- ORCID: 0000-0002-2292-6635
AD  - Department of Biochemistry, School of Life Sciences, Central University of 
      Rajasthan, Ajmer, Rajasthan, India.
LA  - eng
GR  - 17-54-45059/Russian Foundation for Basic Research, Russia/
GR  - INT/RUS/RFBR/P-256/Department of Science and Technology, India/
PT  - Journal Article
DEP - 20210104
PL  - United States
TA  - J Biochem Mol Toxicol
JT  - Journal of biochemical and molecular toxicology
JID - 9717231
RN  - 0 (Neoplasm Proteins)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Breast Neoplasms/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cholesterol/*biosynthesis
MH  - *Dopamine/analogs & derivatives/pharmacology
MH  - Epithelial-Mesenchymal Transition/*drug effects
MH  - Female
MH  - HEK293 Cells
MH  - Humans
MH  - MAP Kinase Signaling System/*drug effects
MH  - Neoplasm Proteins/metabolism
OTO - NOTNLM
OT  - EMT
OT  - ERK signaling
OT  - arachidonoyl dopamine
OT  - breast cancer
OT  - cellular cholesterol
OT  - cholesterol regulatory genes
OT  - stemness
EDAT- 2021/01/05 06:00
MHDA- 2021/07/28 06:00
CRDT- 2021/01/04 09:21
PHST- 2020/11/04 00:00 [revised]
PHST- 2020/08/29 00:00 [received]
PHST- 2020/12/11 00:00 [accepted]
PHST- 2021/01/05 06:00 [pubmed]
PHST- 2021/07/28 06:00 [medline]
PHST- 2021/01/04 09:21 [entrez]
AID - 10.1002/jbt.22693 [doi]
PST - ppublish
SO  - J Biochem Mol Toxicol. 2021 Apr;35(4):e22693. doi: 10.1002/jbt.22693. Epub 2021 
      Jan 4.