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

Nakhjavani Nakhjavani,Hardingham Hardingham,Yool Yool,Palethorpe Palethorpe,Smith Smith,Townsend Townsend,Tomita Tomita,Price Price,Pei Pei

doi:10.3390/ph12030117

Nakhjavani Nakhjavani, Hardingham Hardingham + Show 7 more

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https://doi.org/10.3390/ph12030117

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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.

Highlights

Ginsenosides are a class of natural triterpenoid saponins with the general structure of an aglycone steroid backbone and a glycoside side chain
Neither of the Rg3 epimers inhibited the proliferation of the HCC1143 or DU4475 cell lines
Higher levels of aquaporin 1 (AQP1) expression in breast tumours have been correlated with a triple negativity, poorer prognosis of the disease and higher tumour grade [33,43]

Summary

Introduction

Ginsenosides are a class of natural triterpenoid saponins with the general structure of an aglycone steroid backbone and a glycoside side chain They are extracted from the plant Panax ginseng Meyer, commonly known as ginseng, and play an important role in the medicinal effects of ginseng extract [1,2]. Many papers refer to Rg3 as a single molecule and report the effects of Rg3, rather than a specific epimer, it is noteworthy that Rg3, like other ginsenosides, has two epimers: 20(S)-ginsenoside Rg3 (SRg3) and 20(R)-ginsenoside Rg3 (RRg3). Each of these epimers has distinct pharmacological actions, intracellular targets, effects and efficacies. The SRg3 epimer activates caspases in the human gastric cancer cell line [19] and inhibits Ca2+, Na+ and K+ ion channels [20], while the RRg3 epimer has antioxidant properties to combat cyclophosphamide-induced cellular stress [3]

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