Abstract
Ginsenosides are the principal active components of ginseng and are considered attractive candidates for combination cancer therapy because they can kill tumors and have favorable safety profiles. However, the overall benefit of ginsenosides remains unclear, particularly in cancer immunosurveillance, considering the controversial results showing repression or promotion of immune responses. Here we identify a potentiating role of ginsenoside F1 (G-F1) in cancer surveillance by natural killer (NK) cells. Among 15 different ginsenosides, G-F1 most potently enhanced NK cell cytotoxicity in response to diverse activating receptors and cancer cells. G-F1 also improved cancer surveillance in mouse models of lymphoma clearance and metastatic melanoma that rely on NK cell activity. G-F1-treated NK cells exhibited elevated cytotoxic potential such as upregulation of cytotoxic mediators and of activation signals upon stimulation. NK cell potentiation by G-F1 was antagonized by insulin-like growth factor (IGF)-1 blockade and recapitulated by IGF-1 treatment, suggesting the involvement of IGF-1. Thus, our results suggest that G-F1 enhances NK cell function and may have chemotherapeutic potential in NK cell-based immunotherapy. We anticipate our results to be a starting point for further comprehensive studies of ginsenosides in the immune cells mediating cancer surveillance and the development of putative therapeutics.
Highlights
Ginseng, the root of Panax ginseng C
We reveal that ginsenoside F1 (G-F1), a deglycosylated metabolite of ginsenoside Rg1 (G-Rg1), potentiates natural killer (NK) cell cytotoxicity in a direct and insulin-like growth factor 1 (IGF-1)dependent mechanism, providing a clue for the mysterious efficacy of ginsenosides in NK cell activation
G-Rg1 augmented the degranulation of NK cells against K562 cells (Figure S1A), and this increase was statistically significant (Figure S1B). These analyses revealed that six other ginsenosides (G-F2, G-Rb1, G-Rg3, G-Rh2, G-F1, and G-Rg2) have the potential to enhance the degranulation of NK cells
Summary
A. Meyer, has been a core component of traditional herbal medicine, especially in China and Korea, owing to the belief that it is a tonic and panacea [1,2,3]. Meyer, has been a core component of traditional herbal medicine, especially in China and Korea, owing to the belief that it is a tonic and panacea [1,2,3] It is among the most widely used herbal remedies for various disorders worldwide. The pharmacological properties of ginseng are considered to be mainly attributable to ginsenosides, which are triterpene saponins consisting of a steroidal backbone with sugar moieties [4, 5]. Ginsenosides differ from each other in the position, number, and type of sugar moieties, and such diversity is believed to underlie their diverse therapeutic potentials [4, 5, 7]
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