Ginsenoside compound K, not Rb1, possesses potential chemopreventive activities in human colorectal cancer

Abstract

Ginsenoside compound K (C-K) is an intestinal microbiota metabolite of ginsenoside Rb1, a major constituent in American ginseng. However, previous ginseng anticancer observations were largely focused on ginseng parent compounds but not metabolites, and anti-colorectal cancer studies on C-K were limited. This study investigated the antiproliferative effects of C-K when compared to those of Rb1, and the related mechanisms of action, in HCT-116 and SW-480 colorectal cancer cells. The effects of Rb1 and C-K on the proliferation of HCT-116 and SW-480 human colorectal cancer cells were compared using an MTS assay. Cell cycle and cell apoptosis were assayed using flow cytometry. Enzymatic activities of caspases were determined by colorimetric assay, and interactions of C-K and caspases were explored by docking analysis. C-K showed significant antiproliferative effects in HCT-116 and SW-480 cells at concentrations of 30–50 μM. At the same concentrations, Rb1 did not show any effects, while C-K arrested the cells in the G1 phase, and significantly induced cell apoptosis. Compared to HCT-116 (p53 wild type), the p53 mutant cell line SW-480 was more sensitive to C-K as assessed by cell cycle regulation and apoptosis induction. C-K activated expression of caspases 8 and 9, consistent with docking analysis. The docking data suggested that C-K forms hydrogen bonds with Lys-253, Thr-904 and Gly-362 in caspase 8, and with Thr-62, Ser-63 and Arg-207 in caspase 9. C-K, but not its parent ginsenoside Rb1, showed significant antiproliferative and pro-apoptotic effects in human colorectal cancer cells. These results suggest that C-K could be a potentially effective anti-colorectal cancer agent.

Determination of American ginseng saponins and their metabolites in human plasma, urine and feces samples by liquid chromatography coupled with quadrupole time-of-flight mass spectrometry

“…Metabolic profiles of ginseng by enteric microbiota have been reported in animals [12, 13], and the actions of selected biotransformed metabolites have been elucidated [14]. For example, compound K, a major metabolite in the protopanaxadiols group, has a better bioactivity than its parent compound, ginsenoside Rb 1 [15]. In an in vitro study we observed that human enteric microbiota metabolized ginseng parent compounds into 25 metabolites [16].…”

Deglycosylation of wogonoside enhances its anticancer potential

“…Similar results were also observed in our recent ginsenoside studies. [13,17,24] Our data demonstrated that deglycosylation is a promising approach to increase S. baicalensis glycosides’ anticancer potential.…”

“…After treatment for 24 h, cell lysates were collected and expression levels of caspases 3, 8, and 9 were determined by ELISA analysis. [13] …”

“…[9–11] After deglycosylation, the newly-formed compounds may have more potent anticancer activities. [12,13] …”

American Ginseng Attenuates Colitis-Associated Colon Carcinogenesis in Mice: Impact on Gut Microbiota and Metabolomics

“…We previously observed that after oral administration, parent ginseng compounds were biotransformed by the enteric microbiome to metabolites such as Rg3, Rh1, CK and PPD (16, 17). We have also shown that these ginseng metabolites have potential anticancer effects on CRC (31-33). In this study, we evaluated the effects of oral American ginseng on AOM/DSS-induced colitis and colorectal carcinogenesis, and the subsequent changes in metabolomics and gut microbiota profiles.…”