Trametes versicolor — formerly known as Coriolus versicolor and Polyporus versicolor — is an extremely common polypore mushroom which can be found throughout the world. Versicolor means ‘of several colours’ and it is true that this mushroom is found in a wide variety of different colours. T. versicolor is commonly called Turkey Tail in the United States because of its resemblance to the tail of the wild turkey. T. versicolor is recognized as a medicinal mushroom in Chinese medicine under the name yun zhi (simplified Chinese: ??, traditional Chinese: ??). In China and Japan T. versicolor is used as in immunoadjuvant therapy for cancer.
Mushrooms have traditionally been valued in Asia for their nutritional and medicinal qualities. The Coriolus versicolor or “Turkey Tail” mushroom has been investigated in numerous laboratory, animal and human clinical studies. Most of these studies have demonstrated that it does appear to have significant antimicrobial, antiviral and antitumor properties when used as a supplement to chemotherapy and/or radiotherapy. Human trials have included randomization, a process that decreases bias, but only one has used blinding, which would make them even more protected against biases.
The anti-cancer and immune stimulating properties of Coriolus versicolor have been attributed to two extracts from its cultured mycelium (thread-like extensions). These extracts are both protein-bound polysaccharides known as polysaccharide K (PSK) and polysaccharide-peptide (PSP). Hot water is required to extract these active components.
Yun Zhi Polysaccharides (PSP) is a new type of BRM (Biological Response Modifier) extracted from the deep layer cultivated mycelia of Cov-1 strain of Yun Zhi (Coriolus versicolor). Its active ingredient is a protein bound polysaccharides used in the BRM therapy of tumors. Its characteristics and the general aspects of its research are briefly introduced in this paper
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]
U.S. National Library of Medicine
National Institutes of Health
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Cheuk-Lun Lee, Xiaotong Yang, Jennifer Man-Fan Wan
Department of Zoology, Kardoorie Biological Science Building, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China
Received 24 December 2003; accepted 5 October 2004
Polysaccharopeptide (PSP) derives from the medicinal mushroom Coriolus versicolor is considered a biological response modifier with potential pharmaceutical applications. Significant literatures support the immune and anticancer functions of PSP; however, standardization is of big concern because variable biotechnological factors can affect both the chemical and biological properties of PSP. In this study, the extracts of PSP obtained at different days from the Coriolus versicolor culture were tested in vitro for their immune function on human normal peripheral blood mononuclear cells (PBMC) and cytotoxicity on the human leukemia Molt 4 cells. Over the 10-days culture period, both biomass and peptide/polysaccharide content were increased with time. The increase in proliferation index of PBMC and their production of interleukin 1 beta (IL-1_), tumor necrosis factor alpha (TNF-_) and gamma interferon (IFN-_) in the presence of PHA strengthens the correlation between culture duration and biological potency of PSP. The growth inhibition of the Molt 4 cells by PSP also depended on its maturity. Flow cytometry analysis on cell cycle and cell death (apoptosis) of Molt 4 cells indicated that the anticancer mechanism of PSP is related to its ability to induce S-phase cell arrest and apoptosis, respectively. Together, these results suggest that monitor the harvest duration is critical for the quality control of polysaccharopeptide in the biotechnological industry.
These results suggest that the immunological functions of macrophages is related to the activity of glutathione peroxidase. The non-specific immune-polysaccharide might protect macrophages by the damage induced by reactive oxygen species by enhancing anti-oxidative capacity.
Jin-Xu Zhou, Xin-li Shen, Zu-ming Shen, Xiao-yu Li Department of Pharmacology I Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai 200031
Polysaccharide peptide of Coriolus versicolor (PSP) is a new anti-tumor and immunomodulating drug. In this paper PSP showed direct inhibition on the cell proliferation of sarcoma 180 in vitro and inhibitory effect on the growth of murine sarcoma 180 in vivo. Owing to its direct cytotoxic effect was not strong, but at lower concentrations (10-20ug/ml) of PSP promoted the proliferation of T and pre-T cells of mouse thymus, increased the thymus weight, provided more number of lymphocytes, prevented the involuation of thymus in tumor bearing mice and antagonized the anti-tumor action of PSP combined with antilymphocyte serum. It is suggested the principal mechanism of anti-tumor activity of PSP was T-cell mediated cytotoxicity.
It has been known that some polysaccharides and polysaccharide peptide isolated from various natural sources, especially isolated from Basiodiomycetes have certain anti-tumor activities. The polysaccharide contained a main chain of an alpha and beta (1-4) glucan and a tightly bound 15-38% polypeptides (PSP) isolated from Coriolus versicolor (Fr) Quel. (Cov-1) by Professor Qing-yao Yang also exhibited antitumor action against mouse sarcoma 180 in vitro and in vivo. Recent experiments suggest three possible mechanism by which these PSP might act: (1) Potentiating of T-cell mediated cytotoxicity which killed more number of target-tumor cells. (2) Definite concentration of PSP produced direct cytotoxic activity in vitro. (3) Induction of tumorcidal macrophages killed more cancer cells. In this paper the antitumor action of PSP and its possible mechanism are reported
Department of Radiation Medicine (Radiobiology Program), Loma Linda University and Medical Center, Loma Linda, Calif. 92354, USA. firstname.lastname@example.org
Long-term control of high-grade brain tumors is rarely achieved with current therapeutic regimens. The major goal of this study was to determine whether polysaccharopeptide (PSP), a crude polysaccharide peptide extract derived from Coriolus versicolor, a fungus, could enhance the effects of radiation against glioma cells in culture and in xenografted tumors in vivo. PSP significantly augmented radiation-induced damage to C6 rat glioma cells in vitro. Nude mice injected subcutaneously with the C6 cells were treated with PSP (injected intraperitoneally at 2 mg/injection) and radiation (2 Gy/fraction, 8 Gy in total) using three different time-dose protocols. Tumor volumes were consistently smaller in all treated groups compared to the non-treated tumor-bearing controls except in one group which received PSP prior to tumor implantation. The administration of radiation alone resulted in the slowest tumor progression, whereas PSP alone had no effect. Furthermore, PSP in combination with radiation treatment did not increase radiation efficacy. Natural killer cell, lymphocyte and granulocyte counts in blood and spleen were significantly higher in PSP-treated animals, demonstrating that PSP has protective effects on immunological function. Collectively, these results warrant further investigation to determine if PSP can be effectively utilized to upregulate immune responsiveness in case of neoplasia and other diseases in which immunosuppression is a prominent feature.
F Zeng, CC Hon, WH Sit, KY Chow, RK Hui, IK Law, VW Ng, XT Yang, FC Leung, JM Wan.
Department of Zoology, The University of Hong Kong, Hong Kong, SAR, P.R. China.
Proteins and peptide bound polysaccharides (PSP) extracted from Basidiomycetous fungi are widely used in cancer immunotherapy and recently demonstrated to induce apoptosis in cancer cells in vitro. In order to provide the molecular pharmacological mechanisms of PSP on human cancer cells, we investigated the gene expression profiles of PSP-treated apoptotic human promyelotic leukemic HL-60 cells using ResGen 40k IMAGE printed cDNA microarray. In total 378 and 111 transcripts were identified as differentially expressed in the apoptotic cells by at least a factor of 2 or 3, respectively. Our data show that PSP-induced apoptosis in HL-60 cells might be mediated by up-regulation of early transcription factors such as AP-1, EGR1, IER2 and IER5, and down-regulation of NF-kappaB transcription pathways. Other gene expression changes, including the increase of several apoptotic or anti-proliferation genes, such as GADD45A/B and TUSC2, and the decrease of a batch of phosphatase and kinase genes, may also provide further evidences in supporting the process of PSP induced apoptosis in cancer cells. Some of the well-characterized carcinogenesis-related gene transcripts such as SAT, DCT, Melan-A, uPA and cyclin E1 were also alternated by PSP in the HL-60 cells. These transcripts can be employed as markers for quality control of PSP products on functional levels. The present study provides new insight into the molecular mechanisms involved in PSP-induced apoptosis in leukemic HL-60 cells analyzed by cDNA microarray.
Departments of Biochemistry and Anatomy, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Coriolus versicolor polysaccharopeptide has been reported to exert immunomodulatory and antitumor actions. The present study showed that it exhibits analgesic activity in the hot-plate test upon intraperitoneal administration to ICR mice. 2. It did not affect ovarian steroidogenesis, ovulation and midterm gestation in mice. It did not exert an adverse effect on mouse embryonic development either, as evidenced by the lack of an effect on somite number, axial length and the incidence of abnormalities in heartbeat, yolk sac circulation, optic vesicle, otic vesicle, shape of body axis, forelimb buds, branchial apparatus, cranial neural tube and head size. 3. Its analgesic activity would add to its attribute as an immunomodulatory and antitumor drug.