Nakhjavani Maryam, Palethorpe Helen M, Tomita Yoko, Smith Eric, Price Timothy J, Yool Andrea J, Pei Jinxin V, Townsend Amanda R, Hardingham Jennifer E
Molecular Oncology, Basil Hetzel Institute, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia.
Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia.
Pharmaceuticals (Basel). 2019 Aug 1;12(3):117. doi: 10.3390/ph12030117.
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). The 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.
人参皂苷Rg3（Rg3）有两种差向异构体，20(S)-人参皂苷Rg3（SRg3）和20(R)-人参皂苷Rg3（RRg3），虽然已有报道称Rg3本身具有抗癌特性，但关于不同差向异构体的抗癌作用的研究报道较少。本研究旨在通过基于细胞的增殖、凋亡、细胞周期阻滞、迁移和侵袭检测方法，研究Rg3差向异构体对三阴性乳腺癌（TNBC）细胞系的立体选择性作用。分子对接显示Rg3与水通道蛋白1（AQP1）水通道相互作用（结合分数为-9.4 kJ/mol）。采用卵母细胞表达系统研究Rg3差向异构体对AQP1水通透性的影响。通过定量聚合酶链反应（PCR）比较TNBC细胞系中AQP1的表达。结果显示，只有SRg3抑制AQP1水通量，并抑制MDA-MB-231细胞（100 μM）的增殖，这是由于细胞周期阻滞在G0/G1期。SRg3抑制趋化因子诱导的MDA-MB-231细胞迁移。MDA-MB-231细胞中AQP1的表达高于HCC1143或DU4475细胞系。这些结果表明AQP1在该细胞系的增殖和趋化因子诱导的迁移中起作用。与SRg3相比，RRg3具有更强的效力和效果，可抑制MDA-MB-231细胞的迁移和侵袭。Rg3在高表达AQP1的细胞系MDA-MB-231中具有立体选择性抗癌作用。
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