Effect of sun ginseng potentiation on epirubicin and paclitaxel-induced apoptosis in human cervical cancer cells – Accepted Manuscript

Abstract: Background: Sun ginseng (SG), a specific formulation of quality-controlled red ginseng contains approximately equal amounts of three major ginsenosides (RK1, Rg3, and Rg5), which reported has anti-tumor promoting activities in animal models.Method: MTT assay was employed to assess whether SG can potentiate the anticancer activity of epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells; Apoptosis status was analyzed by Annexin V-FITC and PI and analyzed by flow cytometry; Apoptosis pathway was studied by analysis of caspas-3, -8, and -9 activation, mitochondrial accumulation of Bax and Bak, and cytochrome c release.Results: SG remarkably enhances cancer cell death induced by epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells. Results of the mechanism study highlighted the cooperation between SG and epirubicin or paclitaxel in activating caspases-3 and -9 but not caspase-8. Moreover, SG significantly increased the mitochondrial accumulation of both Bax and Bak triggered by epirubicin or paclitaxel as well as the subsequent release of cytochrome c in the targeted cells.Conclusions: SG significantly potentiated the anticancer activities of epirubicin and paclitaxel in a synergistic manner. These effects were associated with the increased mitochondrial accumulation of both Bax and Bak that led to an enhanced cytochrome c release, caspase-9/-3 activation, and apoptosis. Treating cancer cells by combining epirubicin and paclitaxel with SG may prove to be a novel strategy for enhancing the efficacy of the two drug types.

Ginsenoside fractions regulate the action of monocytes and their differentiation into dendritic cells – Accepted Manuscript

Abstract: Background: Ginseng, the root of Panax ginseng, has been extensively used in traditional oriental medicine and is a modern pharmaceutical reagent for the prevention of various human diseases, including cancer. Ginsenosides are the major active component of ginseng and exhibit immunomodulatory effects. However, the mechanism and function underlying such effects have not been fully elucidated, especially in human monocytes and dendritic cells (DCs).Methods: We investigated the immunomodulatory effect of ginsenosides from the root of Panax ginseng on CD14+ monocytes purified from human adult peripheral blood mononuclear cells (PBMC) and differentiation into DCs that affect CD4+ T cell activity.Results: The results showed that tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 increased in monocytes upon treatment with ginsenoside fractions through phosphorylation of ERK1/2 (pERK1/2) and JNK, but not p38 MAP kinase. Interestingly, TNF-α production and phosphorylation of ERK1/2 and JNK decreased in lipopolysaccharide (LPS)-sensitized monocytes upon treatment with ginsenoside fractions. Next, we confirmed that DCs derived from CD14+ monocytes in the presence of ginsenoside fractions (Gin-DCs) contained decreased levels of the co-stimulatory molecules, CD80 and CD86. In the presence of ginsenoside fractions, expression of these co-stimulatory molecules decreased in LPS-treated DCs compared with LPS-treated DCs in the absence of ginsenoside fractions. Furthermore, Gin-DCs treated with LPS could not induce proliferation and IFN-γ production of CD4+ T cells at co-culture of Gin-DCs with CD4+ T cells.Conclusion: These results suggest that ginsenoside fractions from the ginseng root suppress cytokine production and maturation of DCs treated with LPS, resulting in the down-regulation of CD4+ T cells.