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Medical Studies

Molecular characterization of Coriolus versicolor PSP-induced apoptosis in human promyelotic leukemic HL-60 cells using cDNA microarray.

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.[…]

Immunomodulatory activities of Yunzhi and Danshen in post-treatment breast cancer patients.

Breast cancer is the most common cancer among women worldwide. Discomfort and fatigue are usually arisen from anticancer therapy such as surgery, radiotherapy, chemotherapy, hormonal therapy, or combination therapy, because of the suppressed immunological functions. Yunzhi (Coriolus versicolor) can modulate various immunological functions in vitro, in vivo, and in human clinical trials. Danshen (Salvia miltiorrhiza) has been shown to benefit the circulatory system by its vasodilating and anti-dementia activity. The purpose of this clinical trial was to evaluate the immunomodulatory effects of Yunzhi-Danshen capsules in post-treatment breast cancer patients. Eighty-two patients with breast cancer were recruited to take Yunzhi [50 mg/kg body weight, 100% polysaccharopeptide (PSP)] and Danshen (20 mg/kg body weight) capsules every day for a total of 6 months. EDTA blood samples were collected every 2 months for the investigation of immunological functions. Flow cytometry was used to assess the percentages and absolute counts of human lymphocyte subsets in whole blood. Plasma level of soluble interleukin-2 receptor (sIL-2R) was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that the absolute counts of T-helper lymphocytes (CD4+), the ratio of T-helper (CD4+)/T suppressor and cytotoxic lymphocytes (CD8+), and the percentage and the absolute counts of B-lymphocytes were significantly elevated in patients with breast cancer after taking Yunzhi-Danshen capsules, while plasma slL-2R concentration was significantly decreased (all p < 0.05). Therefore, the regular oral consumption of Yunzhi-Danshen capsules could be beneficial for promoting immunological function in post-treatment of breast cancer patients.[…]

Lack of prevention of large intestinal cancer by VPS, an extract of Coriolus versicolor mushroom.

Cancer prevention studies were conducted with VPS, a hot water extract of the Coriolus versicolor (CV) mushroom, in female Swiss mice. The extract was administered in the diet for life to the animals. Three groups of mice received the following treatments: a). 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) was administered as 10 weekly subcutaneous injections of 20 microg/g body weight, starting at 9 weeks of age; b). VPS was given at a 2% dose level starting at 7 weeks of age followed by 1,2-DMH, as described in group a; c). 1,2-DMH was administered as described in group a followed by VPS at a 2% dose level starting at 21 weeks of age. The number of animals with large intestinal tumors and the total number of these tumors were: a). 30,321; b). 29,359; and c). 28,415. These differences are not statistically significant. Because extracts of the CV mushroom are used by cancer patients as nutritional supplements in the U.S., and particularly in the Orient, the present negative result should caution its users.[…]

Effects of different fungal elicitors on growth, total carotenoids and astaxanthin formation by Xanthophyllomyces dendrorhous.

Six fungal elicitors prepared from Rhodotorula rubra, Rhodotorula glutinis, Panus conchatus, Coriolus versicolor, Mucor mucedo, Mortieralla alpina M-23 were examined to determine their effects on the growth, total carotenoids and astaxanthin formation by Xanthophyllomyces dendrorhous. The results showed that different fungal elicitor could cause diversely stimulating effects. Among the fungal elicitors tested, the M. mucedo elicitor concentration of 30 mg l(-1) promoted the biomass and total carotenoids yield most remarkably, resulting in 69.81+/-6.00% and 78.87+/-4.15% higher than the control, respectively. At the concentration of 30 mg l(-1), R. glutinis elicitor stimulated the highest astaxanthin yield with a 90.60+/-5.98% increase compared to the control. The R. rubra elicitor concentration of 30 mg l(-1) resulted in the optimal total carotenoids and astaxanthin content to be 42.24+/-0.49% and 69.02+/-0.72% higher than the control, respectively. At the concentration of 30 mg l(-1), R. rubra elicitor gave the highest increase in the ratio of astaxanthin in total carotenoids by 18.85+/-0.11% of the control.[…]

Nutrient movement and mycelial reorganization in established systems of Phanerochaete velutina, following arrival of colonized wood resources.


The effect of arrival of wood resources, pre-colonized by Coriolus versicolor, Phlebia radiata, Stereum hirsutum, and Vuilleminia comedens, on mycelial systems of Phanerochaete velutina was studied in trays of nonsterile soil in the laboratory over 5 months. Morphological responses were quantified non-destructively using image analysis. In a parallel series of experiments, nutrient movement was also quantified non-destructively using (32)P monitoring with a scintillation probe and subsequently by destructively harvesting after 155 days. The presence of a fungus occupying a newly arriving resource had major effects on deployment of biomass and on the uptake and allocation of phosphorus in the established Pha. velutina system. The effects varied depending on the species occupying the new resource. Hyphal coverage was greater in the half of the system to which new resources were added. Following addition of new resources, there was massive redeployment of biomass away from regions with no new resource when the new resource was (1) uncolonized, (2) colonized by V. comedens, or (3) colonized by S. hirsutum (although to a lesser extent with the latter), but not with others. (32)P was taken up by Pha. velutina both in the vicinity of the inoculum and the new resource and was translocated to the new resource from both sites of uptake; however, the local supply contributed most. Bidirectional translocation also occurred. The results are discussed in relation to mycelial foraging strategies, nutrient translocation, and partitioning within mycelial cord systems.[…]

Decolorization of bleach plant effluent by mucoralean and white-rot fungi in a rotating biological contactor reactor.


Bleach plant effluents from the pulp and paper industry generated during bleaching with chlorine-containing chemicals are highly colored and also partly toxic due to the presence of chloro-organics, hence the need for pretreatment prior to discharge. In a rotating biological contactor (RBC) reactor effluent decolorization was studied using Coriolus versicolor, a white-rot fungus and Rhizomucor pusillus strain RM7, a mucoralean fungus. Decolorization by both fungi was directly proportional to initial color intensities. It was found that the extent of decolorization was not adversely affected by color intensity, except at the lowest level tested. It was shown that decolorization of 53 to 73% could be attained using a hydraulic retention time of 23 h. With R. pusillus, 55% of AOX were removed compared to 40% by C. versicolor. Fungal treatment with both R. pusillus and C. versicolor rendered the effluent essentially nontoxic. Addition of glucose to decolorization media stimulated color removal by C. versicolor, but not with R. pusillus. Ligninolytic enzymes (manganese peroxidase and laccase) were only detected in effluent treated by C. versicolor. It seems that there are definite differences in the decoloring mechanisms between the white-rot fungus (adsorption + biodegradation) and the mucoralean fungus (adsorption). This aspect needs to be investigated in greater detail to verify the mode responsible for the decolorization activity in both types of fungi.[…]

Effects of polysaccharide peptide (PSP) from Coriolus versicolor on the pharmacokinetics of cyclophosphamide in the rat and cytotoxicity in HepG2 cells

Polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, has been shown to restore the immunological effects against cyclophosphamide-induced immuno-suppression, although the mechanism(s) involved remain uncertain. This study investigated the PSP-cyclophosphamide interaction by studying the effects of PSP on the pharmacokinetic of cyclophosphamide in the rat and the effect of PSP on the cytotoxic effects of cyclophosphamide on a cancer cell line (HepG2 cells). In the pharmacokinetic studies in the rat, acute pre-treatment of PSP (4 micromol/kg/day, i.p.) decreased the clearance (CL) of cyclophosphamide by 31%, with a concomitant increase in the area under concentration-time curve (AUC) by 44%, and prolongation of the plasma half-life (T(1/2)) by 43%. Sub-chronic pre-treatment of PSP (2 micromol/kg/day, i.p., 3 days) decreased the CL of cyclophosphamide by 33%, with a concomitant increase in the AUC by 50%, and prolongation of the plasma T(1/2) by 34%. In cytotoxicity studies using HepG2 cells, non-toxic dose of PSP (1-10 microM) enhanced the cytotoxicity of cyclophosphamide. PSP at 10 microM further decreased HepG2 cell viability by 22% compared to when cyclophosphamide was present alone. In summary, PSP enhanced the cytotoxic effect of cyclophosphamide on a cancer cell line in vitro and altered the pharmacokinetics of cyclophosphamide in vivo in the rat. Both of these effects may be beneficial in the use of PSP as an adjunct to cyclophosphamide treatment.[…]

Polysaccharide peptides from COV-1 strain of Coriolus versicolor induce hyperalgesia via inflammatory mediator release in the mouse.

Polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, has been widely used as an adjunct to cancer chemotherapy and as an immuno-stimulator in China. In this study, the anti-nociceptive effects of PSP were investigated in two different pain models in the mouse. In the acetic acid-induced writhing model, initial studies showed that PSP decreased the number of acetic acid-induced writhing by 92.9%, which, by definition, would constitute an analgesic effect. However, further studies showed that PSP itself induced a dose-dependent writhing response. Studies on inflammatory mediator release showed that PSP increased the release of prostaglandin E2, tumor necrosis factor-alpha, interleukin-1beta, and histamine in mouse peritoneal macrophages and mast cells both in vitro and in vivo. The role of inflammatory mediator release in PSP-induced writhing was confirmed when diclofenac and dexamethasone decreased the number of writhing responses by 54% and 58.5%, respectively. Diphenhydramine totally inhibited the PSP-induced writhing. In the hot-plate test, PSP dose-dependently shortened the hind paw withdrawal latency, indicative of a hyperalgesic effect. The hyperalgesic effect was reduced by pretreatment with the anti-inflammatory drugs. In conclusion, the PSP-induced hyperalgesia was related to activation of peritoneal resident cells and an increase in the release of inflammatory mediators.[…]

[Trypsin-like proteinases and trypsin inhibitors in fruiting bodies of higher fungi]

The activity of trypsin-like proteinases and trypsin inhibitors was measured in fruiting bodies of various species of basidial fungi (Basidiomycetes). Fruiting bodies of all fungi contained these enzymes, with the exceptions of polypore (Coriolus versicolor (Fr.) Karst) and hedgehog fungus (Hericium erinaceus (Fr.) Quel), belonging to the families Polyporaceae and Hericiaceae, respectively, in which the enzyme activities were barely detectable. The activity of trypsin-like proteinases was the highest in fruiting bodies of Boletaceae and Agaricaceae. Fruiting bodies of all fungi contained trypsin inhibitors. The highest activity of trypsin inhibitors was detected in basidiomycetes of the families Boletaceae, Agaricaceae, and Pleurotaceae, including Boletus castanus (Fr.) Karst, orange-cap boletus (Leccinum aurantiacum (Fr.) Sing), and brown-cap boletus (Leccinum melanum (Fr.) Karst).[…]

Evaluation of cytotoxic and mutagenic effects of Coriolus versicolor and Funalia trogii extracts on mammalian cells.

This study examined the in vitro cytotoxic activities of standardized aqueous bioactive extracts prepared from Coriolus versicolor and Funalia trogiiATCC 200800 on HeLa and fibroblast cell lines using a MTT (3-[4,5-dimetiltiazol-2-]-2-5-difeniltetrazolium bromide) cytotoxicity assay. F. trogii and C. versicolor extracts were cytotoxic to both cell lines. At 10 microL treatment level, F. trogii and C. versicolor extracts inhibited proliferation of HeLa cancer cells by 71.5% and 45%, respectively, compared with controls. Toxicity was lower toward normal fibroblasts. In the latter case, treatment at 10 microL level with F. trogii and C. versicolor extracts reduced cell proliferation by 51.3% and 38.7%, respectively. In separate experiments, the mitotic index (MI) obtained with 3 microL treatment level of unheated extracts of the two fungi was comparable to the MI value obtained by treatment with 4 microg/mL MMC (anticancer agent mitomycin-C). A significant induction of sister chromatid exchange (SCE) was observed in normal cultured lymphocytes treated with MMC (4 microg/mL). MMC treatment reduced replication index compared with treatment with unheated F. trogii extract and negative controls (p 0.05). Laccase and peroxidase enzyme activities in F. trogii extract were implicated in their inhibitory effect on cancer cells. F. trogii extract was concluded to have antitumor activity.[…]