The protein-bound polysaccharide PSK was tested for the ability to activate human natural killer (NK) cells. When blood lymphocytes and purified CD3-CD16 ÷ large granular lymphocytes (LGL) were treated in vitro overnight with PSK, they demonstrated enhanced NK cell activity against K562. The PSK-activated killer cells also lysed NK-resistant targets and freshly isolated autologous and allogeneic tumor cells. The PSK effect was observed with concentrations that could be obtained in the blood of cancer patients receiving oral administration of PSK. PSK-induced enhancement of NK activity was not abrogated by monoclonal antibodies (mAb) that neutralized interferon (IFN)o~, IFN3,, or interleukin-2 (IL-2). In addition, mAb reactive with p55 (~ chain) or p75 (/3 chain) glycoproteins of IL-2 receptors had no effects on PSK-enhanced NK activity even when used simultaneously. These results indicate that the PSK could activate human NK cells independently of IFN and IL-2/IL-2R systems.
Mushrooms are known for their nutritional and medicinal value (Breene, 1990) and also for the diversity of bioactive compounds they contain. The mushroom Coriolus versicolor (Yun Zhi) was recorded in the Compendium of Materia Medica by Li Shi Zhen during the Ming Dynasty in China, as being beneficial to health and able to bring longevity if consumed regularly. Various products derived from this mushroom and claimed to have medicinal value are commercially available. Among them, PSK (Sakagami et al., 1991) and PSP are the most prominent. It is the intent of this article to summarize research data pertaining to PSP.
PSK (Sakagami et al., 1991) and PSP are two chemically related products of the mushroom Coriolus versico~or isolated from deeplayer cultivated mycelia of the COV-1 and CM-101 strains, by Chinese and Japanese investigators, respectively. The similarities and differences of the two products have been pointed out by the Fungi Research Institute (1993a). Both possess a molecular weight of approximately 100 kDa and their polypeptide moieties are rich in aspartic acid and glutamic acid. Monosaccharides with o~-1,4 and [3-1,3 glucosidic linkages constitute the pol~saccharide moieties of PSP and PSK: fucose is found in the latter¢ whereas arabinose and rhamnose occur in the former. Both PSP and PSK have been found to be immunoenhancing and effective against tumor cells.
Effects of the immunomodulator PSK on the metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) to 5-fluorouracil (5-FU) were examined in 10 patients with advanced gastric cancer and who had undergone curative resection. PSK is a protein-bound preparation, extracted from Coriolus versicolor and belongs to Basidiomycetes. The 5-FU concentration in the plasma was 0.024 micrograms/ml at 15 min after the intravenous injection of 400 mg of tegafur and the area under the curve of 5-FU was 0.58 micrograms.h/ml. Following administration of PSK, 3 g/day for 8-14 months, there was no change in the plasma level of 5-FU, in any patient. As the clinical dose of PSK had no apparent influence on the metabolism of tegafur to 5-FU, the combination of PSK and tegafur can be prescribed to treat patients with advanced gastric cancer.
We found that PSK has an antiviral effect on human immunodeficiency virus (HIV) in vitro. One of the mechanisms of this effect is attributable to the inhibition of binding of HIV with lymphocytes. Here, we found that PSK inhibits reverse transcriptase in a non-competitive way in vitro. Such inhibition may be important in its anti-HIV effect as well as its inhibitory effect on the binding of HIV with lymphocytes.