Anti-cancer effects of an optimised combination of ginsenoside rg3 epimers on triple negative breast cancer models Nakhjavani, Maryam, Smith, E, Palethorpe, HM, Tomita, Y, Yeo, K, Price, TJ, Townsend, AR and Hardingham, JE 2021, Anti-cancer effects of an optimised combination of ginsenoside rg3 epimers on triple negative breast cancer models, Pharmaceuticals, vol. 14, no. 7, pp. 1-20, doi: 10.3390/ph14070633. Attached Files Name Description MIMEType Size Downloads Title Anti-cancer effects of an optimised combination of ginsenoside rg3 epimers on triple negative breast cancer models Author(s) Nakhjavani, Maryam Smith, E Palethorpe, HM Tomita, Y Yeo, K Price, TJ Townsend, AR Hardingham, JE Journal name Pharmaceuticals Volume number 14 Issue number 7 Article ID 633 Start page 1 End page 20 Total pages 20 Publisher MDPI AG Place of publication Basel, Switzerland Publication date 2021 ISSN 1424-8247 1424-8247 Keyword(s) Epimer ginsenoside Rg3 metastasis nod scid gamma mice response surface methodology triple negative breast cancer Summary Key problems of chemotherapies, as the mainstay of treatment for triple-negative breast cancer (TNBC), are toxicity and development of tumour resistance. Using response surface methodology, we previously optimised the combination of epimers of ginsenoside Rg3 (Rg3) for anti-angiogenic action. Here, we show that the optimised combination of 50 µM SRg3 and 25 µM RRg3 (C3), derived from an RSM model of migration of TNBC cell line MDA-MB-231, inhibited migration of MDA-MB-231 and HCC1143, in 2D and 3D migration assays (p < 0.0001). C3 inhibited mammosphere formation efficiency in both cell lines and decreased the CD44+ stem cell marker in the mammospheres. Molecular docking predicted that Rg3 epimers had a better binding score with IGF-1R than with EGFR, HER-2 or PDGFR, and predicted an mTOR inhibitory function of Rg3. C3 affected the signalling of AKT in MDA-MB-231 and HCC1143 mammospheres. In a mouse model of metastatic TNBC, an equivalent dose of C3 (23 mg/kg SRg3 + 11 mg/kg RRg3) or an escalated dose of 46 mg/kg SRg3 + 23 mg/kg RRg3 was administered to NSG mice bearing MDA-MB-231-Luc cells. Calliper and IVIS spectrum measurement of the primary and secondary tumour showed that the treatment shrunk the primary tumour and decreased the load of metastasis in mice. In conclusion, this combination of Rg3 epimers showed promising results as a potential treatment option for TNBC patients. Language eng DOI 10.3390/ph14070633 Field of Research 1115 Pharmacology and Pharmaceutical Sciences HERDC Research category C1 Refereed article in a scholarly journal Free to Read? Yes Persistent URL http://hdl.handle.net/10536/DRO/DU:30159019 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, 09:34:39 EST Mon, 22 Nov 2021, 15:16:48 EST Mon, 22 Nov 2021, 15:23:16 EST Fri, 26 Nov 2021, 15:14:15 EST Sat, 04 Dec 2021, 01:48:09 EST Tue, 15 Feb 2022, 08:41:45 EST Tue, 15 Feb 2022, 13:45:59 EST Tue, 15 Feb 2022, 13:50:40 EST Filtered Full Citation counts:   Cited 0 times in TR Web of Science Cited 3 times in Scopus Search Google Scholar Access Statistics: 51 Abstract Views, 0 File Downloads  -  Detailed Statistics Created: Mon, 22 Nov 2021, 09:34:39 EST