The Anti-Tumor Effect and Underlying Apoptotic Mechanism of Ginsenoside Rk1 and Rg5 in Human Liver Cancer Cells

Abstract

Ginsenoside Rk1 and Rg5 are minor ginseng saponins that have received more attention recently because of their high oral bioavailability. Each of them can effectively inhibit the survival and proliferation of human liver cancer cells, but the underlying mechanism remains largely unknown. Network pharmacology and bioinformatics analysis demonstrated that G-Rk1 and G-Rg5 yielded 142 potential targets, and shared 44 putative targets associated with hepatocellular carcinoma. Enrichment analysis of the overlapped genes showed that G-Rk1 and G-Rg5 may induce apoptosis of liver cancer cells through inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signal pathways. Methyl thiazolyl tetrazolium (MTT) assay was used to confirm the inhibition of cell viability with G-Rk1 or G-Rg5 in highly metastatic human cancer MHCC-97H cells. We evaluated the apoptosis of MHCC-97H cells by using flow cytometry and 4′,6-diamidino-2-phenylindole (DAPI) staining. The translocation of Bax/Bak led to the depolarization of mitochondrial membrane potential and release of cytochrome c and Smac. A sequential activation of caspase-9 and caspase-3 and the cleavage of poly(ADP-ribose) polymerase (PARP) were observed after that. The levels of anti-apoptotic proteins were decreased after treatment of G-Rk1 or G-Rg5 in MHCC-97H cells. Taken together, G-Rk1 and G-Rg5 promoted the endogenous apoptotic pathway in MHCC-97H cells by targeting and regulating some critical liver cancer related genes that are involved in the signal pathways associated with cell survival and proliferation.

Network Pharmacology of Ginseng (Part II): The Differential Effects of Red Ginseng and Ginsenoside Rg5 in Cancer and Heart Diseases as Determined by Transcriptomics

“…These conclusions are in line with other reports on the antitumor activity of ginseng and purified ginsenosides [ 19 , 23 , 25 , 26 , 36 , 39 , 40 , 41 , 42 , 43 , 44 ].…”

“…Numerous studies of purified ginsenosides show their potential efficacy in treating cancer and other diseases [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ], suggesting that the total extract or powdered roots have similar or probably better therapeutic effectiveness [ 23 , 24 , 25 , 26 ]. However, clinical evidence supporting this suggestion in comparative studies is missing [ 27 , 28 ].…”

(20S) Ginsenoside Rh2 Exerts Its Anti-Tumor Effect by Disrupting the HSP90A-Cdc37 System in Human Liver Cancer Cells

“…Therefore, (20S) G-Rh2 holds promise as a multi-target drug for cancer therapy. In addition, we found other ginsenosides such as ginsenoside Rk1 and ginsenoside Rg5 also had strong inhibitory effects on cancer cells [ 59 ], but the anti-tumor mechanisms of these natural compounds remained unclear. Whether these ginsenosides exert their anti-tumor effect by targeting HSP90A or other proteins will be further investigated in our future studies.…”

Phytotherapy in Integrative Oncology—An Update of Promising Treatment Options

“…A red ginseng extract enriched with the ginsenoside Rg3 suppressed cell division of lung cancer cells and induced mitochondria-dependent apoptosis [ 163 ]. The ginsenosides Rk1 and Rg5 promoted apoptosis in human liver cancer cells, as well [ 164 ]. Furthermore, ginsenoside (20S)-protopanaxatriol inhibited Akt/mTor signalling pathway in triple-negative breast cancer (TNBC) cells, inducing non-protective autophagy.…”