Category Archives: Why It Works

Effects of OK-432 (picibanil) on the estrogen receptors of MCF-7 cells and potentiation of antiproliferative effects of tamoxifen in combination with OK-432.

Aoyagi H, Iino Y, Takeo T, Horii Y, Morishita Y, Horiuchi R.

Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.

Abstract

OK-432 (picibanil), a streptococcal preparation, has a strong biological response modifier (BRM) function and is expected to produce clinical improvement and prolongation of survival in treated cancer patients in Japan. We were interested in whether OK-432 augments estrogen receptor (ER) levels in breast cancer. To investigate the effect of the BRMs on cellular growth and the characteristics of ER and progesterone receptors (PgR) in the human breast cancer cell line MCF-7, we used OK-432, Krestin (PSK), a protein-bound polysaccharide extracted from Coriolus versicolor, and lentinan, a fungal branched (1…3)-beta-D-glycan. OK432 and PSK dose dependently inhibited DNA synthesis of MCF-7 cells, and the 50% inhibitory concentrations of OK-432 and PSK were 1.2 KE (klinische Einheit, clinical unit)/ml and 200 micrograms/ml, respectively. Lentinan showed no direct anticancer effect in vitro. We found that OK-432 induced a 2-fold increase in ER levels in MCF-7 cells at 0.005 KE/ml, but not in PgR. Lentinan and low-dose PSK did not change ER or PgR levels, but high-dose PSK decreased ER and PgR. We also studied the combined effect of OK-432 and antiestrogens, tamoxifen (TAM) and DP-TAT-59. The combined treatment with OK-432 and TAM showed an additive inhibitory effect on MCF-7 cells. These results suggest that OK-432 may augment the therapeutic effect of TAM in breast cancer.

PMID: 9260604 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/9260604

In vitro chemopreventive effects of plant polysaccharides (Aloe barbadensis miller, Lentinus edodes, Ganoderma lucidum and Coriolus versicolor).

Kim HS, Kacew S, Lee BM.

Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Changan-ku, Chunchun-dong, Kyunggi-do, Suwon 440-746, Korea.

Abstract

A plant polysaccharide, Aloe gel extract, was reported to have an inhibitory effect on benzo[a]pyrene (B[a]P)-DNA adduct formation in vitro and in vivo. Hence, chemopreventive effects of plant polysaccharides [Aloe barbadensis Miller (APS), Lentinus edodes (LPS), Ganoderma lucidum (GPS) and Coriolus versicolor (CPS)] were compared using in vitro short-term screening methods associated with both initiation and promotion processes in carcinogenesis. In B[a]P-DNA adduct formation, APS (180 micrograms/ml) was the most effective in inhibition of B[a]P binding to DNA in mouse liver cells. Oxidative DNA damage (by 8-hydroxydeoxyguanosine) was significantly decreased by APS (180 micrograms/ml) and CPS (180 micrograms/ml). In induction of glutathione S-transferase activity, GPS was found to be the most effective among plant polysaccharides. In screening anti-tumor promoting effects, APS (180 micrograms/ml) significantly inhibited phorbol myristic acetate (PMA)-induced ornithine decarboxylase activity in Balb/3T3 cells. In addition, APS significantly inhibited PMA-induced tyrosine kinase activity in human leukemic cells. APS and CPS significantly inhibited superoxide anion formation. These results suggest that some plant polysaccharides produced both anti-genotoxic and anti-tumor promoting activities in in vitro models and, therefore, might be considered as potential agents for cancer chemoprevention.

PMID: 10426820 [PubMed – indexed for MEDLINE]Free Article

http://www.ncbi.nlm.nih.gov/pubmed/10426820

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The use of mushroom glucans and proteoglycans in cancer treatment.

Kidd PM.

Abstract

Immunoceuticals can be considered as substances having immunotherapeutic efficacy when taken orally. More than 50 mushroom species have yielded potential immunoceuticals that exhibit anticancer activity in vitro or in animal models and of these, six have been investigated in human cancers. All are non-toxic and very well tolerated. Lentinan and schizophyllan have little oral activity. Active Hexose Correlated Compound (AHCC) is poorly defined but has shown early clinical promise. Maitake D-Fraction has limited proof of clinical efficacy to date, but controlled research is underway. Two proteoglycans from Coriolus versicolor – PSK (Polysaccharide-K) and PSP (Polysaccharide-Peptide – have demonstrated the most promise. In Japanese trials since 1970, PSK significantly extended survival at five years or beyond in cancers of the stomach, colon-rectum, esophagus, nasopharynx, and lung (non-small cell types), and in a HLA B40-positive breast cancer subset. PSP was subjected to Phase II and Phase III trials in China. In double-blind trials, PSP significantly extended five-year survival in esophageal cancer. PSP significantly improved quality of life, provided substantial pain relief, and enhanced immune status in 70-97 percent of patients with cancers of the stomach, esophagus, lung, ovary, and cervix. PSK and PSP boosted immune cell production, ameliorated chemotherapy symptoms, and enhanced tumor infiltration by dendritic and cytotoxic T-cells. Their extremely high tolerability, proven benefits to survival and quality of life, and compatibility with chemotherapy and radiation therapy makes them well suited for cancer management regimens.

PMID: 10696116 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/10696116

Immunomodulation and anti-cancer activity of polysaccharide-protein complexes.

Ooi VE, Liu F.

Department of Biology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.

Abstract

In the last three decades, numerous polysaccharides and polysaccharide-protein complexes have been isolated from mushrooms and used as a source of therapeutic agents. The most promising biopharmacological activities of these biopolymers are their immunomodulation and anti-cancer effects. They are mainly present as glucans with different types of glycosidic linkages such as (1–>3), (1–>6)-beta-glucans and (1–>3)-alpha-glucans, and as true herteroglycans, while others mostly bind to protein residues as polysaccharide-protein complexes. Three antitumor mushroom polysaccharides, i.e. lentinan, schizophyllan and protein-bound polysaccharide (PSK, Krestin), isolated respectively, from Lentinus edodes, Schizophyllum commune and Coriolus versicolor, have become large market items in Japan. Lentinan and schizophyllan are pure beta-glucans, whereas PSK is a protein-bound beta-glucan. A polysaccharide peptide (PSP), isolated from a strain of Coriolus versicolor in China, has also been widely used as an anti-cancer and immunomodulatory agent. Although the mechansim of their antitumor action is still not completely clear, these polysaccharides and polysaccharide-protein complexes are suggested to enhance cell-mediated immune responses in vivo and in vitro and act as biological response modifiers. Potentiation of the host defense system may result in the activation of many kinds of immune cells that are vitally important for the maintenance of homeostasis. Polysaccharides or polysaccharide-protein complexes are considered as multi-cytokine inducers that are able to induce gene expression of vaious immunomodulatory cytokines and cytokine receptors. Some interesting studies focus on investigation of the relationship between their structure and antitumor activity, elucidation of their antitumor mechanism at the molecular level, and improvement of their various biological activities by chemical modifications.

PMID: 10702635 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/10702635

Dr. Mark Flannery Joins inLife LLC’s Board as Medical Advisor

Irvine, California inLife, LLC distributors of science-based Health & Wellness products, today announced Dr. Mark Flannery joins inLife’s Board as Medical Advisor. Dr. Flannery, who specializes in the treatment of autoimmune disorders and chronic illness using advanced nutritional therapies is a Diplomate of the College of Clinical Nutrition, a Diplomate of the Chiropractic Board of Clinical Nutrition, and a Certified Nutrition Specialist by the Certification Board for Nutrition Specialists, today joins inLife to bring awareness and enlightenment to the public of inLife’s new immunological nutritional supplement, inForce Immune Builder.

Dr. Flannery who assists his patients in achieving their optimal health by focusing on correcting the imbalances in their physiology says, “After much research and analization of inLife inForce Immune Builder’s main ingredient Coriolus versicolor, I am very proud to be part of a company that is on the verge of helping many, many people realize their true health potential. In reviewing the research and viewing many of the testimonials so far submitted to inLife I am convinced that inForce Immune Builder should be part of everyone’s daily nutritional routine.” Dr. Flannery will also soon be seen interviewed by Cristina Ferrare on inLife’s soon-to-be-viewed national infomercial about the science behind inForce Immune Builder.

About Coriolus Versicolor

The Coriolus Versicolor mushroom is one of the most widely studied supplements for its immune building properties. Worldwide, there have been over 400 animal and human studies on Coriolus versicolor with over a dozen placebo-based human trials conducted in the west. Traditionally, the Coriolus versicolor mushroom (known as Yun-zhi or cloud mushroom in China) has been used in China for several thousand years because of its immune boosting capabilities. In the 1980s, Dr. Yang conducted further studies and was able to isolate a much more potent strain using a different, alcohol-based extraction process. The result was Polysaccharopeptide or PSP. In the United States, top-ranked hospital and research institutes have reported that Coriolus versicolor helps boost the body’s immune systems with limited side effects and safety of daily oral doses for extended periods of time. In addition, Coriolus versicolor and its potential positive effects has been studied very closely by M.D. Anderson, University of Texas, Loma Linda University, Beth Israel Deaconess Medical Center (a teaching hospital of Harvard Medical School) , The University of San Diego, Sloan-Kettering Center (New York), and Bastyr University (Kenmore, Washington) just to name a few.

inLife Immune Builder with PSP and PSK

inLife offers Coriolus versicolor as a Daily Dietary Supplement in capsule form to help maintain and stimulate the body’s immune system. Coriolus versicolor and its high-potency extracts, PSK and PSP are among the most widely studied supplements for their immune building properties. One would be hard-pressed to find another immune boosting product that has had more research completed or positive comments associated with it. The amount of worldwide comments and studies is compelling. InForce Immune Builder is a proprietary blend of both Polysaccharide-K (PSK) and Polysaccharopeptide (PSP). Both offer much needed immune building assistance and they can be taken on a daily basis. The products are bottled in the United States in an FDA registered bottling facility that is CGMP compliant (Current Good Manufacturing Practices).

About inLife, LLC

Founded in 2007, inLife has been very successful in bringing to market products that have efficacies that are soundly based on scientific research. inLife products are now available in the U.S. as well as the U.K, Canada and Spain. For more information on inForce Immune Builder and the company, please review www.myinlife.com. For further details on inForce, journalists may contact Thomas Kiklas directly at 949-648-2525.

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Founded in 2007, inLife has been very successful in bringing to market products that have efficacies that are soundly based on scientific research. For further details on inForce, journalists may contact Thomas Kiklas directly at 949-648-2525.

Click here to download this press release.

Anticancer effects and mechanisms of polysaccharide-K (PSK): implications of cancer immunotherapy.

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]

http://www.ncbi.nlm.nih.gov/pubmed/12168863

Coriolus versicolor: a medicinal mushroom with promising immunotherapeutic values.

Chu KK, Ho SS, Chow AH.

School of Pharmacy, Faculty of Medicine, Chinese University of Hong Kong, Shatin, NT.

Abstract

Coriolus versicolor (CV) is a medicinal mushroom widely prescribed for the prophylaxis and treatment of cancer and infection in China. In recent years, it has been extensively demonstrated both preclinically and clinically that aqueous extracts obtained from CV display a wide array of biological activities, including stimulatory effects on different immune cells and inhibition of cancer growth. The growing popularity of aqueous CV extracts as an adjunct medical modality to conventional cancer therapies has generated substantial commercial interest in developing these extracts into consistent and efficacious oral proprietary products. While very limited information is available on the physical, chemical, and pharmacodynamic properties of the active principles present in these extracts, there has been sufficient scientific evidence to support the feasibility of developing at least some of these constituents into an evidence-based immunodulatory agent. In this article, the background, traditional usage, pharmacological activities, clinical effects, adverse reactions, active constituents, and regulatory aspects of CV are reviewed. Presented also in this review are the current uses and administration, potential drug interactions, and contraindication of aqueous extracts prepared from CV.

PMID: 12211223 [PubMed – indexed for MEDLINE]

Polysaccharopeptides of Coriolus versicolor: physiological activity, uses, and production.

Cui J, Chisti Y.

Institute of Technology and Engineering PN456, Massey University, Private Bag 11 222, 5320, Palmerston North, New Zealand.

Abstract

The protein-bound polysaccharides or polysaccharopeptides produced by Coriolus versicolor are effective immunopotentiators, which are used to supplement the chemotherapy and radiotherapy of cancers and various infectious diseases. Antitumor activity of polysaccharopeptides has been documented. Several kinds of protein-bound polysaccharides have been shown to be produced by the white rot fungus, C. versicolor. Although some of these polymers are structurally distinct, they are not distinguishable in terms of their physiological activity. This review focuses on the physiologically active polysaccharopeptides of C. versicolor. In nature, C. versicolor occurs as a mushroom body, but the fungus can be grown as mycelial biomass in submerged culture in bioreactors. Mushrooms gathered in the wild, cultivated mushrooms, and the mycelial biomass of submerged culture are used to produce the polysaccharopeptides. Submerged cultures are typically carried out in batches lasting 5-7 days and at 25-27 degrees C. Hot water extraction of the biomass is used to recover the thermostable polysaccharopeptides that are concentrated, purified, and dried into a powder for medicinal use. In view of the documented physiological benefits of these compounds, extensive research is underway on the structure, composition, production methods, and use of new C. versicolor strains for producing the therapeutic biopolymers. Properties, physiological activity, recovery, and purification of the bioactive polysaccharopeptides are discussed.

PMID: 14499133 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/14499133

Evaluation of Argentinean white rot fungi for their ability to produce lignin-modifying enzymes and decolorize industrial dyes.

Lau CB, Ho CY, Kim CF, Leung KN, Fung KP, Tse TF, Chan HH, Chow MS.

School of Pharmacy, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. claralau@cuhk.edu.hk

Abstract

Coriolus versicolor (CV), also known as Yunzhi, is one of the commonly used Chinese medicinal herbs. Although recent studies have demonstrated its antitumour activities on cancer cells in vitro and in vivo, the exact mechanism is not fully elucidated. Hence, the objective of this study was to examine the in vitro cytotoxic activities of a standardized aqueous ethanol extract prepared from Coriolus versicolor on a B-cell lymphoma (Raji) and two human promyelocytic leukemia (HL-60, NB-4) cell lines using a MTT cytotoxicity assay, and to test whether the mechanism involves induction of apoptosis. Cell death ELISA was employed to quantify the nucleosome production resulting from nuclear DNA fragmentation during apoptosis. The present results demonstrated that CV extract at 50 to 800 microg/ml dose-dependently suppressed the proliferation of Raji, NB-4, and HL-60 cells by more than 90% (p < 0.01), with ascending order of IC50 values: HL-60 (147.3 +/- 15.2 microg/ml), Raji (253.8 +/- 60.7 microg/ml) and NB-4 (269.3 +/- 12.4 microg/ml). The extract however did not exert any significant cytotoxic effect on normal liver cell line WRL (IC50 > 800 microg/ml) when compared with a chemotherapeutic anticancer drug, mitomycin C (MMC), confirming the tumour-selective cytotoxicity. Nucleosome productions in HL-60, NB-4 and Raji cells were significantly increased by 3.6-, 3.6- and 5.6-fold respectively upon the treatment of CV extract, while no significant nucleosome production was detected in extract-treated WRL cells. The CV extract was found to selectively and dose-dependently inhibit the proliferation of lymphoma and leukemic cells possibly via an apoptosis-dependent pathway.

PMID: 15183073 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/15158509

Treatment of cancer with mushroom products.

Monro JA.

Breakspear Hospital, Hemel Hempstead, Herts, United Kingdom. jmonro@breakspearmedical.com

Abstract

Cancer has been attributed to 3 causes: pollution, infection, and poor nutrition. Conventional treatments include surgery, chemotherapy, and radiotherapy. The author proposes that immunotherapy also be considered. Among other environmental influences, dietary deficiencies and carcinogenic viral infections must be investigated and treated wherever possible. It has been suggested that mushrooms, in particular, have a structure that is immunomodulatory because it resembles the proteoglycan structure in the human extracellular matrix, and both are metabolically active. Inasmuch as mitochondria have a bacterial origin, proteoglycans may have a mushroom origin. The author describes a study which shows that natural killer cells can double in number with 8 wk of treatment with Coriolus versicolor. Also described is an epidemiological survey of cancer deaths among Flammulina velutipes farmers in Japan, which found that the mushroom farmers had lower rates of cancer deaths than controls who were not involved in mushroom farming.

PMID: 15259434 [PubMed – indexed for MEDLINE]