The Anti-tumor Activities And Mechanisms Of Ginseng Polysaccharides

Panax ginseng C.A. Meyer has been used as a medicinal plant in Asian countries over thousands years. Polysaccharides are one of its active components. The anti-tumor activities of ginseng polysaccharides have been subjected to a number of investigations, but the structure-activity relatioship and the underlying mechanisms are not well elucidated. In this paper, we tested the effect of ginseng polysaccharides on anti-tumor activity, and demonstrated on structure-activities and mechanisms in detail.The water-soluble polysaccharides (WGP) were extracted from the roots of P. ginseng according to our previous method. WGP was further fractionated into three types of water soluble polysaccharides: the starch-like glucans, homogalacturonan (HG)- and arabinogalactans (AG)-rich pectins. Besides, ginseng pectin WGPA was treated by Endo-PG. The hydrolysates were fractionated by anion-exchange and gel-permeation chromatography, resulting in rhamnogalacturonan I (RG-I)-rich pectins.The availability of these structurally defined fractions and pure polysaccharides enabled us to study the effects of individual component. We cultured different cells in the presence of different type of ginseng polysaccharides and detected cell proliferation. The results highlighted the different anti-proliferation associated with different types of ginseng polysaccharides. A neutral fraction WGPN had no inhibition at concentration; while ginseng pectin exerted variable inhibition.First, we examined the anti-tumor activities of ginseng polysaccharides WGP, starch-like glucan WGPN and ginseng pectin WGPA using S-180 mouse models and found all these fractions exerted inhibition on S-180 tumor growth. Meanwhile, the three fractions could promote the immune systems of tumor- bearing mice. Thus, the mechanisms of WGP, WGPN and WGPA might involve the modulation of host immune defenses. Besides, RG-I-rich pectins RG-I-2, RG-I-3B and RG-I-4 were also tested for anti-tumor and immunological activity on S180 sarcoma mice. The results showed they could inhibit the growth of transplanted S180 tumor cells and had a little effect on the host immunity. The mechanisms of RG-I-rich pectins might involve the modulation of host immune defenses, but other mechanisms might exist.And then, we selected one homogenous fraction from each type i.e. WGPN from the starch-like glucan, WGPA-2-RG from the AG type pectin, and WGPA-3-HG from the HG type pectin, to study their anti-tumor activities and the structure-activity relationship. In addition, we also selected WGPA-1-HG because it was enriched with both AG- and HG-domains. The order of inhibition rate was WGPA-1-HG? WGPA-2-RG?WGPN?WGPA-3-HG. Then, we investigated the mechanisms related to their anti-tumor activities. We examined tumor-bearing mice fed with various polysaccharides for their lymphocytes proliferation, macrophage phagocytosis and NO production. The immune activities of these ginseng polysaccharides were following this order: WGPN?WGPA-1-HG≥WGPA-2-RG?WGPA-3-HG. Apparently, immune stimulation could not explain the anti-tumor activities of these type polysaccharides. Other mechanisms might exist. So we examined the S-180 tumors grown in mice fed with various polysaccharides for their cell cycle and apoptosis and we found that fractions WGPA-1-HG and WGPA-3-HG could induce apoptosis, WGPA-2-RG affected tumor cell cycle, WGPN did not have effect on the tumor. To further understand the actions of WGPA-2-RG, WGPA-1-HG, and WGPA-3-HG on tumors, we carried out in vitro experiments with cultured S-180 cells. The results of the in vitro experiments were generally consistent with those in vivo, WGPA-2-RG, WGPA-1-HG and WGPA-3-HG but not WGPN did have effects on the tumors. We also found that butyrate induced apoptosis and cell cycle arrest in a similar way as that fund in vivo. Thus, in addition to the intact polysaccharides, their degradation and fermentation products might also be involved in direct tumor inhibition.As mentioned above, different type of ginseng polysaccharide had different effects and acted by different mechanisms. The starch-like glucan inhibit tumor growth via enhancing the host immune defenses, the pectin inhibited tumor growth via both the modulation of the host immune defenses and the direct tumor inhibition. HG type pectin induced tumor cell apoptosis. AG type pectin affected tumor cell cycle. We noted that fractions with both immune stimulation and tumor interference activities (e.g. WGPA-1-HG and WGPA-2-RG) exerted markedly stronger inhibition than those with either only immune stimulation (e.g. WGPN) or only tumor interference (e.g. WGPA-3-HG) activities.