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Stereoselective Anti-Cancer Activities of Ginsenoside Rg3 on Triple Negative Breast Cancer Cell Models

1
Molecular Oncology, Basil Hetzel Institute, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia
2
Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia
3
Oncology Unit, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2019, 12(3), 117; https://doi.org/10.3390/ph12030117
Received: 15 May 2019 / Revised: 24 July 2019 / Accepted: 29 July 2019 / Published: 1 August 2019
PDF [955 KB, uploaded 1 August 2019]

Abstract

Ginsenoside Rg3 (Rg3) has two epimers, 20(S)-ginsenoside Rg3 (SRg3) and 20(R)-ginsenoside Rg3 (RRg3), and while Rg3 itself has been reported to have anti-cancer properties, few studies have been reported on the anti-cancer effects of the different epimers. The aim was to investigate the stereoselective effects of the Rg3 epimers on triple negative breast cancer (TNBC) cell lines, tested using cell-based assays for proliferation, apoptosis, cell cycle arrest, migration and invasion. Molecular docking showed that Rg3 interacted with the aquaporin 1 (AQP1) water channel (binding score −9.4 kJ mol−1). The Xenopus laevis oocyte expression system was used to study the effect of Rg3 epimers on the AQP1 water permeability. The AQP1 expression in TNBC cell lines was compared with quantitative-polymerase chain reaction (PCR). The results showed that only SRg3 inhibited the AQP1 water flux and inhibited the proliferation of MDA-MB-231 (100 μM), due to cell cycle arrest at G0/G1. SRg3 inhibited the chemoattractant-induced migration of MDA-MB-231. The AQP1 expression in MDA-MB-231 was higher than in HCC1143 or DU4475 cell lines. These results suggest a role for AQP1 in the proliferation and chemoattractant-induced migration of this cell line. Compared to SRg3, RRg3 had more potency and efficacy, inhibiting the migration and invasion of MDA-MB-231. Rg3 has stereoselective anti-cancer effects in the AQP1 high-expressing cell line MDA-MB-231.
Keywords: breast cancer; epimer; stereoselective; Ginsenoside Rg3; triple negative breast cancer breast cancer; epimer; stereoselective; Ginsenoside Rg3; triple negative breast cancer
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Nakhjavani, M.; Palethorpe, H.M.; Tomita, Y.; Smith, E.; Price, T.J.; Yool, A.J.; Pei, J.V.; Townsend, A.R.; Hardingham, J.E. Stereoselective Anti-Cancer Activities of Ginsenoside Rg3 on Triple Negative Breast Cancer Cell Models. Pharmaceuticals 2019, 12, 117.

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