nakhjavani-anticancereffects-2021.pdf (5.44 MB)
Anti-cancer effects of an optimised combination of ginsenoside rg3 epimers on triple negative breast cancer models
journal contribution
posted on 2021-01-01, 00:00 authored by Maryam Nakhjavani, E Smith, H M Palethorpe, Y Tomita, K Yeo, T J Price, A R Townsend, J E HardinghamKey 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.
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Journal
PharmaceuticalsVolume
14Issue
7Article number
633Pagination
1 - 20Publisher
MDPI AGLocation
Basel, SwitzerlandPublisher DOI
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ISSN
1424-8247eISSN
1424-8247Language
engPublication classification
C1 Refereed article in a scholarly journalUsage metrics
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