Anti-angiogenic properties of ginsenoside rg3 epimers: In vitro assessment of single and combination treatments Nakhjavani, Maryam, Smith, E, Yeo, K, Palethorpe, HM, Tomita, Y, Price, TJ, Townsend, AR and Hardingham, JE 2021, Anti-angiogenic properties of ginsenoside rg3 epimers: In vitro assessment of single and combination treatments, Cancers, vol. 13, no. 9, pp. 1-20, doi: 10.3390/cancers13092223. Attached Files Name Description MIMEType Size Downloads Title Anti-angiogenic properties of ginsenoside rg3 epimers: In vitro assessment of single and combination treatments Author(s) Nakhjavani, Maryam Smith, E Yeo, K Palethorpe, HM Tomita, Y Price, TJ Townsend, AR Hardingham, JE Journal name Cancers Volume number 13 Issue number 9 Article ID 2223 Start page 1 End page 20 Total pages 20 Publisher MDPI Place of publication Basel, Switzerland Publication date 2021 ISSN 2072-6694 2072-6694 Keyword(s) angiogenesis AQUAPORIN-1 CANCER CELL-MIGRATION ENDOTHELIAL GROWTH-FACTOR epimer ginsenoside Rg3 HIF-1-ALPHA HYPOXIA Life Sciences & Biomedicine MECHANISMS Oncology optimisation PROLIFERATION response surface methodology Science & Technology STEREOSPECIFICITY TUMOR-GROWTH Summary 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 Language eng DOI 10.3390/cancers13092223 Field of Research 1112 Oncology and Carcinogenesis HERDC Research category C1 Refereed article in a scholarly journal Free to Read? Yes Persistent URL http://hdl.handle.net/10536/DRO/DU:30159017 Document type: Journal Article Collections: Faculty of Health School of Medicine Open Access Collection Related Links Link Description Link to full-text (open access)   Connect to Elements publication management system Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au. Versions Version Filter Type Mon, 22 Nov 2021, 09:34:09 EST Mon, 22 Nov 2021, 15:16:46 EST Mon, 22 Nov 2021, 15:23:14 EST Fri, 26 Nov 2021, 15:14:13 EST Sat, 04 Dec 2021, 01:33:04 EST Sat, 04 Dec 2021, 01:48:07 EST Mon, 24 Jan 2022, 13:13:52 EST Mon, 24 Jan 2022, 15:23:45 EST Mon, 24 Jan 2022, 15:31:00 EST Filtered Full Citation counts:   Cited 1 times in TR Web of Science Cited 3 times in Scopus Search Google Scholar Access Statistics: 31 Abstract Views, 0 File Downloads  -  Detailed Statistics Created: Mon, 22 Nov 2021, 09:34:09 EST