Fisher M, Yang LX.
Radiobiology Laboratory, St. Mary’s Medical Center, California Pacific Medical Center Research Institute, San Francisco
94118, USA.
Abstract
Polysaccharide-K (polysaccharide-Kureha; PSK), also known as krestin, is a unique protein-bound polysaccharide, which
has been used as a chemoimmunotherapy agent in the treatment of cancer in Asia for over 30 years. PSK and
Polysaccharopeptide (PSP) are both protein-bound polysaccharides which are derived from the CM-101 and COV-1 strains
of the fungus Coriolus versicolor by Japanese and Chinese researchers, respectively. Both polysaccharide preparations
have documented anticancer activity in vitro, in vivo and in human clinical trials, though PSK has been researched longer
and has therefore undergone more thorough laboratory, animal and clinical testing. Several randomized clinical trials have
demonstrated that PSK has great potential as an adjuvant cancer therapy agent, with positive results seen in the adjuvant
treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as
an immunotherapy or biological response modifier (BRM). BRMs potentially have the ability to improve the “host versus
tumor response,” thereby increasing the ability of the host to defend itself from tumor progression. The mechanisms of
biological response modification by PSK have yet to be clearly and completely elucidated. Some studies suggest that PSK
may act to increase leukocyte activation and response through up-regulation of key cytokines. Indeed, natural killer (NK)
and lymphocyte-activated killer (LAK) cell activation has been demonstrated in vivo and in vitro, and recent genetic studies
reveal increased expression of key immune cytokines in response to treatment with PSK. An antimetastatic action of PSK
has also been demonstrated and is perhaps attributed to its potential to inhibit metalloproteinases and other enzymes
involved in metastatic activity. PSK has also been shown to cause differentiation of leukemic cells in vitro, and this effect
has been attributed to induction of differentiation cytokines. PSK has further been shown to have antioxidant capacity which
may allow it to play a role as a normal tissue chemo- and radio-protector when used in combination with adjuvant or
definitive chemotherapy and/or radiotherapy in the treatment of cancer, while it may also enable it to defend the host from
oxidative stress. Interestingly, studies have also shown that PSK may actually inhibit carcinogenesis by inhibiting the action
of various carcinogens on vulnerable cell lines. This action of PSK may play a role in preventing second primary tumors
when an inducing agent, such as tobacco or asbestos, is suspected and may also prevent second malignancies due to the
carcinogenic effects of radiotherapy and cytotoxic chemotherapy. Another very important aspect of chemoimmunotherapy,
in general is that it may be used on debilitated patients such as those with AIDS and the elderly who might otherwise be
denied potentially helpful adjuvant cytotoxic chemotherapy. Further determination of the mechanisms of these anti-cancer,
immunostimulating and biological response modifying effects of PSK as well as of other protein-bound polysaccharides is
certainly warranted. Indeed, with modern cellular and molecular biology techniques, a better understanding of the specific
Molecular effects of PSK on tumor cells as well as leukocytes may be determined. Much of the research that has been done
on PSK is outlined in this paper and may serve as a foundation toward determining the mechanisms of action of this and
other protein-bound polysaccharides in the treatment of cancer. This information may open new doors in the development
of novel strategies for the treatment of malignancies using adjuvant immunotherapy in combination with surgery,
chemotherapy and/or radiotherapy.
PMID: 12168863 [PubMed – indexed for MEDLINE]
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