Anti-Cancer Effects of Panax ginseng Berry Polysaccharides via Activation of Immune-Related Cells

Abstract

Panax ginseng has long been used as natural medicine and health food all over the world. Cancer is a major cause of death worldwide and its prognosis likely depends on the immune system during tumor treatment. In this study, ginseng berry polysaccharides were evaluated for their immunostimulant and anti-cancer effects. Ginseng berry polysaccharide portion (GBPP) was used to investigate its effects on anti-complementary activity, peritoneal macrophage activation, and natural killer (NK) cell cytotoxicity. Moreover, both intravenous (i.v.) and oral administration of GBPP prior to B16-BL6 melanoma implantation in mice was evaluated. GBPP significantly increased the anti-complementary activity and cytokine production including interleukin (IL)-6, IL-12, and tumor necrosis factor (TNF)-α, dose-dependently. Splenocytes obtained after i.v. administration of GBPP showed cytolytic activity in Yac-1 cells in proportion to the E/T ratio. In addition, GBPP enhanced the production of interferon (IFN)-γ and granzyme B of NK cells. For the experimental lung cancer, compared with control mice, GBPP delivered by i.v. suppressed cancer by 48% at 100 μg/mouse, while a 37% reduction was achieved by oral administration. Deficient of NK cells in animal model demonstrated that the anti-cancer effect of GBPP was through NK cell activation. Results of this study suggest that ginseng berry polysaccharides, owing to their modulation of the immune response, can be a potential curative applicant for the prevention and treatment of tumors.

Keywords: NK cell; ginseng berry; immunostimulation; macrophage; metastasis; polysaccharide.

Figure 1

Schematic diagram of the preparation of ginseng berry polysaccharide portion (GBPP) from Panax ginseng berry.

Figure 2

Content of arabino-β-D-3,6-galactan (type II arabinogalactan; AG-II) in ginseng berry polysaccharide portion, assessed using single radial gel diffusion and the β-D-glucosyl Yariv reagent.

Figure 3

Anti-complementary activity of the ginseng berry polysaccharide portion from ginseng berry. Anti-complementary activity is presented as 50% inhibition of total complementary hemolysis following Mayer´s method. Polysaccharide−K (PSK), a known immunoactive polysaccharide from Coriolus versicolor, was used as a positive control and medium was used as a negative control (NC). Values are expressed as a mean ± SD of three independent experiments performed in triplicate. ^a–d superscript are significantly different from each other (p < 0.05).

Figure 4

Effect of ginseng berry polysaccharide portion on cytotoxicity (A), and production of cytokines interleukin (IL)-6 (B), IL-12 (C), and tumor necrosis factor-α (D) by murine peritoneal macrophages. Values are expressed as a mean ± SD of three independent experiments performed in triplicate. ^a–fBars not sharing the same superscript are significantly different from each other (p < 0.05).

Figure 5

Effects of i.v. administration of ginseng berry polysaccharide portion on cytolytic activity (A), and production of IFN-γ (B) and granzyme B (C) in splenic natural killer cells. Values are expressed as a mean ± SD of three independent experiments performed in triplicate. ^{A–D,a–c,i–iv}Bars not sharing the same superscript are significantly different from each other (p < 0.05).

Figure 6

The inhibitory effect of ginseng berry polysaccharide portion on lung cancer produced by inoculation with B16-BL6 melanoma cells. (A) Growth rate (%) of lung cancer colonies compared to tumor control (100%). (B) Lung photograph excised in each groups. Means with different superscript letters (a–c) indicate significant differences at p < 0.05 by Duncan’s multiple range tests.

Figure 7

Effect of intravenous administration of ginseng berry polysaccharide portion on cytotoxic T lymphocyte (CTL) activation of normal and natural killer cell depleted BALB/c mice. To deplete NK cells in vivo, mouse anti-asialo GM1 serum was injected into mice 2 days before inoculation of B16-BL6 melanoma cells. Mice were treated with sample (100 μg, intravenous) 1 and 3 days before tumor inoculation. And then, splenocytes were harvested and incubation with B16-BL6 cells. Means with different superscript letters (i–iii, a–c, A–B) indicate significant differences at p < 0.05 by Duncan’s multiple range test.