PMID- 34066403
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210605
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 9
DP  - 2021 May 6
TI  - Anti-Angiogenic Properties of Ginsenoside Rg3 Epimers: In Vitro Assessment of 
      Single and Combination Treatments.
LID - 10.3390/cancers13092223 [doi]
LID - 2223
AB  - Tumour angiogenesis plays a key role in tumour growth and progression. The 
      application of current anti-angiogenic drugs is accompanied by adverse effects 
      and drug resistance. Therefore, finding safer effective treatments is needed. 
      Ginsenoside Rg3 (Rg3) has two epimers, 20(S)-Rg3 (SRg3) and 20(R)-Rg3 (RRg3), 
      with stereoselective activities. Using response surface methodology, we optimised 
      a combination of these two epimers for the loop formation of human umbilical vein 
      endothelial cell (HUVEC). The optimised combination (C3) was tested on HUVEC and 
      two murine endothelial cell lines. C3 significantly inhibited the loop formation, 
      migration, and proliferation of these cells, inducing apoptosis in HUVEC and cell 
      cycle arrest in all of the cell lines tested. Using molecular docking and 
      vascular endothelial growth factor (VEGF) bioassay, we showed that Rg3 has an 
      allosteric modulatory effect on vascular endothelial growth factor receptor 2 
      (VEGFR2). C3 also decreased the VEGF expression in hypoxic conditions, decreased 
      the expression of aquaporin 1 and affected AKT signaling. The proteins that were 
      mostly affected after C3 treatment were those related to mammalian target of 
      rapamycin (mTOR). Eukaryotic translation initiation factor 4E (eIF4E)-binding 
      protein 1 (4E-BP1) was one of the important targets of C3, which was affected in 
      both hypoxic and normoxic conditions. In conclusion, these results show the 
      potential of C3 as a novel anti-angiogenic drug.
FAU - Nakhjavani, Maryam
AU  - Nakhjavani M
AUID- ORCID: 0000-0002-5357-7167
AD  - Molecular Oncology, Basil Hetzel Institute, The Queen Elizabeth Hospital, 
      Woodville South, SA 5011, Australia.
AD  - Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia.
FAU - Smith, Eric
AU  - Smith E
AUID- ORCID: 0000-0003-2958-3492
AD  - Molecular Oncology, Basil Hetzel Institute, The Queen Elizabeth Hospital, 
      Woodville South, SA 5011, Australia.
AD  - Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia.
FAU - Yeo, Kenny
AU  - Yeo K
AUID- ORCID: 0000-0001-5733-0463
AD  - Molecular Oncology, Basil Hetzel Institute, The Queen Elizabeth Hospital, 
      Woodville South, SA 5011, Australia.
AD  - Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia.
FAU - Palethorpe, Helen M
AU  - Palethorpe HM
AUID- ORCID: 0000-0003-3803-5113
AD  - Centre for Cancer Biology, University of South Australia and SA Pathology, 
      Adelaide, SA 5000, Australia.
FAU - Tomita, Yoko
AU  - Tomita Y
AUID- ORCID: 0000-0001-7934-2203
AD  - Molecular Oncology, Basil Hetzel Institute, The Queen Elizabeth Hospital, 
      Woodville South, SA 5011, Australia.
AD  - Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia.
AD  - Oncology Unit, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia.
FAU - Price, Tim J
AU  - Price TJ
AD  - Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia.
AD  - Oncology Unit, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia.
FAU - Townsend, Amanda R
AU  - Townsend AR
AD  - Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia.
AD  - Oncology Unit, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia.
FAU - Hardingham, Jennifer E
AU  - Hardingham JE
AUID- ORCID: 0000-0001-8277-1199
AD  - Molecular Oncology, Basil Hetzel Institute, The Queen Elizabeth Hospital, 
      Woodville South, SA 5011, Australia.
AD  - Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia.
LA  - eng
GR  - Margaret Elcombe/Hospital Research Foundation/
PT  - Journal Article
DEP - 20210506
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8125638
OTO - NOTNLM
OT  - angiogenesis
OT  - epimer
OT  - ginsenoside Rg3
OT  - optimisation
OT  - response surface methodology
COIS- The authors declare no conflict of interest.
EDAT- 2021/06/03 06:00
MHDA- 2021/06/03 06:01
PMCR- 2021/05/06
CRDT- 2021/06/02 01:16
PHST- 2021/03/11 00:00 [received]
PHST- 2021/04/28 00:00 [revised]
PHST- 2021/05/04 00:00 [accepted]
PHST- 2021/06/02 01:16 [entrez]
PHST- 2021/06/03 06:00 [pubmed]
PHST- 2021/06/03 06:01 [medline]
PHST- 2021/05/06 00:00 [pmc-release]
AID - cancers13092223 [pii]
AID - cancers-13-02223 [pii]
AID - 10.3390/cancers13092223 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 May 6;13(9):2223. doi: 10.3390/cancers13092223.