PMID- 28720470
OWN - NLM
STAT- MEDLINE
DCOM- 20170908
LR  - 20170908
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 185
DP  - 2017 Sep 15
TI  - Molecular docking prediction and in vitro studies elucidate anti-cancer activity 
      of phytoestrogens.
PG  - 73-84
LID - S0024-3205(17)30343-0 [pii]
LID - 10.1016/j.lfs.2017.07.015 [doi]
AB  - AIM: The study is aimed at evaluating the chemosensitization and apoptotic effect 
      of aglycone rich extracts of dietary phytoestrogens (derived from soybean and 
      flaxseed) on estrogen receptor positive, MCF-7 and estrogen receptor negative, 
      MDA-MB-231 cells. The extracts show potent activity on both the cell lines, 
      hence, in silico studies have been carried out to find the possible reason for 
      their activity. MAIN METHODS: MTT assay was carried to assess chemosensitization 
      effect and activated caspase-3/7 activity was studied using flow-cytometry and 
      western blotting. In silico studies were carried out using PharmMapper and the 
      top hits were taken up for docking using the Schrodinger software. Top molecular 
      targets were subjected to gene expression studies by qPCR and protein expression 
      using Western blot analysis. KEY FINDINGS: This study reports the apoptotic 
      activity and chemosensitization effect of the phytoestrogens. Molecular docking 
      studies predict AKR1B1 (aldose reductase), HRAS (Harvey rat sarcoma) and GSTP1 
      (glutathione s-transferase pi) as potential molecular targets for genistein, 
      daidzein and secoisolariciresinol, respectively. Gene and protein expression 
      studies show down-regulation of AKR1BI, HRAS and GSTP1 by the extracts. 
      SIGNIFICANCE: The qPCR and western blot analysis results support the 
      computational analyses, and hence genistein, daidzein and secoisolariciresinol 
      may be considered as good candidates for future development into potent 
      inhibitors of the respective protein targets through medicinal chemistry 
      optimization.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Dutta, Shreelekha
AU  - Dutta S
AD  - Department of Biological Sciences, Sunandan Divatia School of Science, SVKM's 
      NMIMS (deemed-to-be) University, Vile Parle (w), Mumbai 400 056, India.
FAU - Kharkar, Prashant S
AU  - Kharkar PS
AD  - Department of Pharmaceutical Chemistry, Shobhaben Pratapbhai Patel School of 
      Pharmacy & Technology Management, SVKM's NMIMS (deemed-to-be) University, Vile 
      Parle (w), Mumbai 400 056, India.
FAU - Sahu, Niteshkumar U
AU  - Sahu NU
AD  - Department of Pharmaceutical Chemistry, Shobhaben Pratapbhai Patel School of 
      Pharmacy & Technology Management, SVKM's NMIMS (deemed-to-be) University, Vile 
      Parle (w), Mumbai 400 056, India.
FAU - Khanna, Aparna
AU  - Khanna A
AD  - Department of Biological Sciences, Sunandan Divatia School of Science, SVKM's 
      NMIMS (deemed-to-be) University, Vile Parle (w), Mumbai 400 056, India. 
      Electronic address: aparna.khanna@nmims.edu.
LA  - eng
PT  - Journal Article
DEP - 20170715
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Butylene Glycols)
RN  - 0 (Isoflavones)
RN  - 0 (Lignans)
RN  - 0 (Phytoestrogens)
RN  - 6287WC5J2L (daidzein)
RN  - DH2M523P0H (Genistein)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 7)
RN  - M8QRJ7JEJH (secoisolariciresinol)
SB  - IM
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Breast Neoplasms/*drug therapy/pathology
MH  - Butylene Glycols/pharmacology
MH  - Caspase 3/metabolism
MH  - Caspase 7/metabolism
MH  - Cell Line, Tumor
MH  - Computer Simulation
MH  - Down-Regulation/drug effects
MH  - Female
MH  - Flow Cytometry
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Genistein/pharmacology
MH  - Humans
MH  - Isoflavones/pharmacology
MH  - Lignans/pharmacology
MH  - MCF-7 Cells
MH  - *Molecular Docking Simulation
MH  - Phytoestrogens/*pharmacology
OTO - NOTNLM
OT  - Aldose reductase
OT  - Breast cancer
OT  - Glutathione s-transferase pi
OT  - H-ras
OT  - Molecular docking
OT  - Phytoestrogens
EDAT- 2017/07/20 06:00
MHDA- 2017/09/09 06:00
CRDT- 2017/07/20 06:00
PHST- 2017/03/25 00:00 [received]
PHST- 2017/07/02 00:00 [revised]
PHST- 2017/07/13 00:00 [accepted]
PHST- 2017/07/20 06:00 [pubmed]
PHST- 2017/09/09 06:00 [medline]
PHST- 2017/07/20 06:00 [entrez]
AID - S0024-3205(17)30343-0 [pii]
AID - 10.1016/j.lfs.2017.07.015 [doi]
PST - ppublish
SO  - Life Sci. 2017 Sep 15;185:73-84. doi: 10.1016/j.lfs.2017.07.015. Epub 2017 Jul 
      15.