Background: Polysaccharide-K (PSK), or Krestin (Sankyo Co., Tokyo, Japan), a mushroom ingredient, has been used as a chemoimmunotherapeutic agent for the treatment of cancers in Asia for over 30 years. Distant metastasis is one of the major problems in treatment for advanced colorectal cancer. There is growing evidence that PSK prevents distant metastases and improves survival rates by 10 to 20% in colorectal, gastric, esophageal, nasopharynx, lung, and breast cancers. However, the mechanism of the direct anti-cancer cell activities of PSK has yet to be elucidated. Methods: To investigate the direct effect on carcinoma cells, we used protein microarrays to analyze expression profiles in a human colorectal adenocarcinoma cell line, SW480 with the mutant p53 gene. We examined the expression of candidate proteins in two cell lines, SW480 and HCT116 with a wild-type p53 gene, and its clinical implication for the prognosis of colorectal cancer patients. Results: Expression of 14 out of 500 proteins was significantly altered (8 upregulated; HDJ-2, TNIK, TRAX, C-NAP1, Moesin, etc. and 6 downregulated; ECA39, Caspase-9/ICE-LAP6/Apaf-3, Synaptotagmin, MAPK2, PMCA2, etc.) after 96 h exposure to 500 mg/ml PSK. We then confirmed the alteration of ECA39 protein, a direct target for c-Myc regulation, in both cell lines, as a candidate relating to anti-metastatic effects of PSK. In immunohistochemical staining, ECA39 was significantly expressed in the tumor tissues with distant metastases compared to the ones without metastases(p<0.00001). Conclusions: Our results suggest that PSK may potentiate anti-metastatic action via ECA39, without disturbing cell-cycle progression, and may deserve a large clinical trial in cancer therapy.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]