Akush Ginekol (Sofiia). 2008;47 Suppl 3:51-3.
[Article in Bulgarian]
Coriolus-MRL is a nutrient adjuvant, which contains biomass of the fungus Coriolus versicolor and is studied to reverse early stages of cervical cancer and to reduce risk factors of reoccurring HPV virus.
PMID: 19449722 [PubMed – indexed for MEDLINE]
Food and Nutritional Science Division, School of Biological Sciences, The University of Hong Kong, Hong Kong SAR, PR China. jmfwan@hkusua.hku.hk
In search of natural bioactive microbial compounds with adjuvant properties, we have previously showed that the polysaccharopeptide (PSP), isolated from Chinese medicinal mushroom Coriolus versicolor, was able to enhance the cytotoxicity of certain S-phase targeted-drugs on human leukemic HL-60 cells via some cell-cycle and apoptotic-dependent pathways. The present study aimed to investigate whether the synergism of mechanisms of PSP with certain chemotherapeutic drugs also applies to human breast cancer. PSP treatment enhanced the cytotoxicity of doxorubicin (Doxo), etoposide (VP-16) but not cytarabine (Ara-C). Bivariate bromodeoxyuridine (BrdUrd)/DNA flow cytometry analysis estimated a longer DNA synthesis time (Ts) for the PSP treated cancerous cells suggesting that PSP enhanced the apoptotic effect of Doxo and VP-16 via creating an S-phase trap in the human breast cancer cell line ZR-75-30. The participation of PSP in the apoptotic machinery of the chemotherapeutic agents was further supported by a reduced ratio of protein expression of Bcl-xL/Bax of the cancer cells. This study provides further insight into the synergistic mechanisms of PSP and supports the hypothesis that the anticancer potentials of PSP is not limited to leukemia but may also be used as an adjuvant therapy for breast cancers.
PMID: 18292947 [PubMed – indexed for MEDLINE]
Harhaji Lj, Mijatovi? S, Maksimovi?-Ivani? D, Stojanovi? I, Momcilovi? M, Maksimovi? V, Tufegdzi? S, Marjanovi? Z, Mostarica-Stojkovi? M, Vucini? Z, Stosi?-Grujici? S.
Department of Immunology, Institute for Biological Research Sinisa Stankovi?, Belgrade University, Belgrade, Serbia.
Numerous studies have shown immunostimulatory and anti-tumor effects of water and standardized aqueous ethanol extracts derived from the medicinal mushroom, Coriolus versicolor, but the biological activity of methanol extracts has not been examined so far. In the present study we investigated the anti-tumor effect of C. versicolor methanol extract (which contains terpenoids and polyphenols) on B16 mouse melanoma cells both in vitro and in vivo. In vitro treatment of the cells with the methanol extract (25-1600 microg/ml) reduced melanoma cell viability in a dose-dependent manner. Furthermore, in the presence of the methanol extract (200 microg/ml, concentration IC(50)) the proliferation of B16 cells was arrested in the G(0)/G(1) phase of the cell cycle, followed by both apoptotic and secondary necrotic cell death. In vivo methanol extract treatment (i.p. 50 mg/kg, for 14 days) inhibited tumor growth in C57BL/6 mice inoculated with syngeneic B16 tumor cells. Moreover, peritoneal macrophages collected 21 days after tumor implantation from methanol extract-treated animals exerted stronger tumoristatic activity ex vivo than macrophages from control melanoma-bearing mice. Taken together, our results demonstrate that C. versicolor methanol extract exerts pronounced anti-melanoma activity, both directly through antiproliferative and cytotoxic effects on tumor cells and indirectly through promotion of macrophage anti-tumor activity.
PMID: 18313195 [PubMed – indexed for MEDLINE]
Jiménez-Medina E, Berruguilla E, Romero I, Algarra I, Collado A, Garrido F, Garcia-Lora A.
Servicio de Análisis Clínicos e Inmunologia, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Av, de las Fuerzas Armadas 2, 18014 Granada, Spain. evajimenez@fundacionhvn.org
BACKGROUND: Protein-bound polysaccharide (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated.
METHODS: The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells.
RESULTS: PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation.
CONCLUSION: These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells.
PMID: 18366723 [PubMed – indexed for MEDLINE]PMCID: PMC2291471Free PMC Article
Ragupathi G, Yeung KS, Leung PC, Lee M, Lau CB, Vickers A, Hood C, Deng G, Cheung NK, Cassileth B, Livingston P.
Laboratory of Tumor Vaccinology, Melanoma and Sarcoma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States. ragupatg@mskcc.org
BACKGROUND: Many widely used botanical medicines are claimed to be immune enhancers. Clear evidence of augmentation of immune responses in vivo is lacking in most cases. To select botanicals for further study based on immune enhancing activity, we study them here mixed with antigen and injected subcutaneously (s.c.). Globo H and GD3 are cell surface carbohydrates expressed on glycolipids or glycoproteins on the cell surface of many cancers. When conjugated to keyhole limpet hemocyanin (KLH), mixed with an immunological adjuvant and administered s.c. the magnitude of the antibody responses against globo H, GD3 and KLH depend largely on the potency of the adjuvant. We describe here the results obtained using this s.c. immunization model with seven botanicals purported to have immune stimulant effects.
METHODS: Groups of 5-10 mice were immunized with globo H-KLH or GD3-KLH mixed with botanical, saline or positive control immunological adjuvant, s.c. three times at 1 week intervals. Antibody responses were measured 1 and 2 weeks after the 3rd immunization. The following seven botanicals and fractions were tested: (1) H-48 (Honso USA Co.), (2) Coriolus versicolor raw water extract, purified polysaccharide-K (PSK) or purified polysaccharide-peptide (PSP) (Institute of Chinese Medicine (ICM)), (3) Maitake extract (Yukiguni Maitake Co. Ltd. and Tradeworks Group), (4) Echinacea lipophilic, neutral and acidic extracts (Gaia Herbs), (5) Astragalus water, 50% or 95% ethanol extracts (ICM), (6) Turmeric supercritical (SC) or hydro-ethanolic (HE) extracts (New Chapter) or 60% ethanol extract (ICM) and (7) yeast beta-glucan (Biotec Pharmacon). Purified saponin extract QS-21 (Antigenics) and semisynthetic saponin GPI-0100 (Advanced BioTherapies) were used as positive control adjuvants. Sera were analyzed by ELISA against synthetic globo H ceramide or GD3 and KLH.
RESULTS: Consistent significant adjuvant activity was observed after s.c. vaccination with the Coriolus extracts (especially PSK), a 95% ethanol extract of Astragalus and yeast beta-glucan, and (to a lesser extent) Maitake. Antibodies against KLH in all cases and against globo H in most cases were induced by these botanicals. Little or no adjuvant activity was demonstrated with H-48 or Echinacea extracts or the Astragalus water extract. Experiments with GD3-KLH as immunogen confirmed the adjuvant activity of the Coriolus, yeast beta-glucan and Astragalus extracts. While extraction with ethanol concentrated the active ingredients in Astragalus, it had no impact on Coriolus where the 90% ethanol precipitate and solute were equally active.
CONCLUSIONS: Some, but not all, botanicals purported to be immune stimulants had adjuvant activity in our model. PSK and Astragalus were surprisingly active and are being further fractionated to identify the most active adjuvant components.
PMID: 18640165 [PubMed – indexed for MEDLINE]PMCID: PMC2565601
WEDNESDAY, Sept. 8 (HealthDay News) — The exact cause of type 1 diabetes is still unknown, but international researchers have found a link between the blood sugar disorder and a network of immune system genes.
Using a genome-wide association study, the researchers found that a certain group of genes that react in response to viral infections were present in both rats and humans, and that those same genes were also associated with a susceptibility to type 1 diabetes.
“Diseases arise as a result of many genetic and environmental factors through gene networks that cause tissue damage,” explained study senior author Dr. Stuart Cook, the group head of molecular and cellular cardiology at the Medical Research Council Clinical Sciences Centre, and a professor of clinical and molecular cardiology at Imperial College in London.
“We used an approach to identify the major control points’ central command of an inflammatory gene network. This led us to uncover hundreds of new genes that might cause diabetes and one major control gene that controls the whole network,” said Cook.
He added that one of the genes belongs to a class of genes that might make a good target for drug therapy in the future.
Results of the study are published in the Sept. 9 issue of Nature.
Each year, more than 30,000 people are diagnosed with type 1 diabetes, formerly known as juvenile diabetes, according to the Juvenile Diabetes Research Foundation (JDRF). People with type 1 diabetes no longer produce enough of the hormone insulin to effectively use the sugars found in carbohydrate-containing foods. To survive, people with type 1 diabetes must take insulin injections or use an insulin pump for the rest of their lives.
Experts believe the disease is an autoimmune disease, which means that the body’s immune system mistakenly turns against healthy cells, such as the insulin-producing cells in the pancreas, and destroys them. People who develop type 1 diabetes are believed to have a genetic susceptibility to the disease that’s then triggered by something in the environment, possibly a virus.
In the current study, the researchers didn’t initially set out to look for type 1 diabetes genes. They started out by looking at a certain group of genes in rats, in this case a network of genes controlled by a gene called interferon regulatory factor 7 (IRF7). IRF7 is like a master switch that controls the genes in its network. The entire network of genes controlled by IRF7 is called the IRF7-driven inflammatory network (IDIN).
The researchers discovered that when there were differences in IRF7, there were also differences in the way other genes expressed themselves.
Cook and his colleagues then searched for a network of genes in humans that might behave the same way. They found an area on chromosome 13q32 that is controlled by a gene called the “Epstein-Barr virus induced gene 2” (Ebi2). This gene appeared to be the human equivalent of the IRF7 gene in rats.
Within this human version of the IDIN, research found a gene called IFIH1, which has been found in other research to be associated with the development of type 1 diabetes.
“Usually, research starts from the genetics and goes to function. Here, they started with a function — [an immune system reaction] — and were looking for a gene,” explained Marie Nierras, director of research and scientific affairs for the JDRF.
“The value of such a result is that if you can get to the same place using more than one pathway, it tends to support the hypothesis,” she said.
In this case, the hypothesis supported is the idea that type 1 diabetes may be triggered by an immune system response to a virus. However, Nierras stressed that this study doesn’t conclusively prove that a virus is the trigger for type 1 diabetes.
“We know better today that this network of genes is involved, and with a network, you have many targets you can test. This research invites us to plan experiments going forward, and opens up many more questions, like ‘If I disrupt this branch of the network, do I disrupt diabetes?’ Or, ‘If you look back at previous research knowing this study’s results, does that help to better explain previous results?'” said Nierras.
Cook said this type of genome-wide association study can be used for other diseases as well, and that his team is hoping to eventually develop a new drug based on the genetic target they discovered.
More information
Learn more about type 1 diabetes and its causes from the U.S. National Library of Medicine.
SOURCES: Stuart Cook, M.D., Ph.D., group head, molecular and cellular cardiology, the Medical Research Council Clinical Sciences Centre, and professor, clinical and molecular cardiology, Imperial College, London; Marie Nierras, Ph.D., director, research and scientific affairs, Juvenile Diabetes Research Foundation, New York City; Sept. 9, 2010, Nature
Copyright © 2010 HealthDay. All rights reserved.
http://www.businessweek.com/lifestyle/content/healthday/642915.html
Maruyama S, Akasaka T, Yamada K, Tachibana H.
Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka, Japan. marushins2003@ybb.ne.jp
Protein-bound polysaccharide-K (PSK) prepared from the basidiomycete Coriolus versicolor has been used as a biological response modifier for the treatment of cancer patients. Many studies describing the immunomodulatory effects and direct anti-cancer effects of PSK have been reported. Most of studies describing the immunomodulatory effects focused on cellular immunity, although there were several studies which focused on humoral immunity where PSK was shown to be able to induce antibody production in vivo. However, even in these humoral immunity studies, it is thought that the enhancement of antibody production was due to the activation of cellular immunity. In this study, we investigated the direct effect of PSK on B cells and discovered that PSK was able to enhance IgM production in the human B cell line BALL-1. Furthermore, BALL-1 was shown to have the characteristic features of B-1a cells, which are independently involved in the primary immune response. These results show that there is a possibility that PSK directly acts on B cells and simultaneously enhances both humoral immunity and cellular immunity.
PMID: 18848763 [PubMed – indexed for MEDLINE]
Lee CL, Sit WH, Jiang PP, So IW, Wan JM.
School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, SAR, China.
The activation of T helper (Th) cell subsets plays an important role in the human immune system. Uncontrolled Th1 and Th2 responses lead to autoimmune and inflammatory diseases, respectively. The identification of agents that modulate the Th1/Th2 cytokines is therefore essential for controlling these diseases. We recently reported that polysaccharopeptide (PSP) from Coriolus versicolor exhibited ciclosporin-like activities to control aberrant T lymphocyte activation. Here, we compared the properties of PSP with ciclosporin on cell proliferation, CD25+ expression, secretion of Th1/Th2 cytokines and activation of mitogen-activated protein kinase (MAPK)p38 and signal transducers and activators of transcription 5 (STAT5) on T cells. The data show that PSP alone suppresses the proliferation of activated T cells. PSP exhibited similar and additive inhibitory effects to ciclosporin to suppress activated T cell proliferation, Th1 cytokines and reduce CD3+/CD25+ cell expression, but not Th2 cytokine expression, which helps the cytokine balance shift towards Th2 dominance. These suppressive actions of PSP involved the MAPKp38 and STAT5 pathways. These findings refine our understanding of the effects of PSP on T lymphocytes and its adjuvant properties with the immunosuppressant ciclosporin for possible control of autoimmune diseases.
PMID: 18957170 [PubMed – indexed for MEDLINE]
Steffensen CL, Stensballe A, Kidmose U, Degn PE, Andersen ML, Nielsen JH.
Department of Food Science, Faculty of Agricultural Sciences, Aarhus University, Research Centre Foulum, Tjele, Denmark. charlotte.l.steffensen@agrsci.dk
Mass spectral analysis demonstrated oligomerization of peptides that had been subjected to oxidation catalysed by Trametes (Coriolus) versicolor laccase. Peptide oligomerization occurred only when cysteines or tyrosines were present in the peptides. MS/MS confirmed the cross-linking in tyrosine-containing peptides to be located between tyrosine residues. Ferulic acid mediated oligomerization of cysteine-containing peptides, but prevented cross-linking of tyrosines when used in the same concentration as the peptides. This suggests an antioxidative effect of ferulic acid in relation to tyrosine oxidation, although incorporation of ferulic acid into peptide oligomers was found in some of the tyrosine-containing peptides. No other modifications to amino acid residues by laccase-catalysed oxidation were observed by mass spectroscopy. Thus, it is suggested that oxidative modifications of other amino acids observed in proteins oxidized by laccase are not major reaction products of laccase-catalysed oxidation.
PMID: 19905979 [PubMed – indexed for MEDLINE]
Wan JM, Sit WH, Yang X, Jiang P, Wong LL.
Agricultural, Food and Nutritional Sciences Division, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China. jmfwan@hkusua.hku.hk.
ABSTRACT:
BACKGROUND: Polysaccharopeptide (PSP) from Coriolus versicolor (Yunzhi) is used as a supplementary cancer treatment in Asia. The present study aims to investigate whether PSP pre-treatment can increase the response of the human leukemia HL-60 cells to apoptosis induction by Camptothecin (CPT).
METHODS: We used bivariate bromodeoxyuridine/propidium iodide (BrdUrd/PI) flow cytometry analysis to measure the relative movement (RM) of the BrdUrd positively labeled cells and DNA synthesis time (Ts) on the HL-60 cell line. We used annexin V/PI flow cytometry analysis to quantify the viable, necrotic and apoptotic cells. The expression of cyclin E and cyclin B1 was determined with annexin V/PI flow cytometry and western blotting. Human peripheral blood mononuclear cells were used to test the cytotoxicity of PSP and CPT.
RESULTS: PSP reduced cellular proliferation; inhibited cells progression through both S and G2 phase, reduced 3H-thymidine uptake and prolonged DNA synthesis time (Ts) in HL-60 cells. PSP-pretreated cells enhanced the cytotoxicity of CPT. The sensitivity of cells to the cytotoxic effects of CPT was seen to be the highest in the S-phase and to a small extent of the G2 phase of the cell cycle. On the other hand, no cell death (measured by annexin V/PI) was evident with the normal human peripheral blood mononuclear cells with treatment of either PSP or CPT.
CONCLUSION: The present study shows that PSP increases the sensitization of the HL-60 cells to undergo effective apoptotic cell death induced by CPT. The pattern of sensitivity of cancer cells is similar to that of HL-60 cells. PSP rapidly arrests and/or kills cells in S-phase and did not interfere with the anticancer action of CPT. PSP is a potential adjuvant to treat human leukemia as rapidly proliferating tumors is characterized by a high proportion of S-phase cells.
PMID: 20423495 [PubMed – in process]PMCID: PMC2874562