The incidence of prostate cancer varies greatly throughout the world; it is highest in African-Americans and lowest in the Asian populations of China, India, and Japan. Geographical differences in both prevalence of latent prostate cancer and mortality have been postulated to be influenced by diverse tumor-promoting and protective factors, both environmental and dietary. Prostate cancer is a tumor with an extremely long latency; the pattern of prostate tumorigenesis, in terms of the display and sequence of appearance of particular molecular or biochemical features, or morphological changes, characterizing different stages of the carcinogenic process, is expected to be heterogeneous. Some insights into tumor heterogeneity and progression can be obtained from studies using cell lines, particularly those derived from different anatomical sites. The present study aims to investigate whether hormone-responsive LNCaP and androgen-refractory JCA-1, PC-3, and DU-145 prostate cancer cells are responsive to Yunzhi (YZ), a proprietary dietary supplement prepared from extracts of Trametes versicolor, also known as Coriolus versicolor (a mushroom consumed by Chinese for its purported health benefits), and to elucidate its mechanism of action. Ethanolic extracts (70%) of YZ significantly reduced LNCaP cell growth, down-regulated the levels of secreted PSA, but had less effects on the expression of intracellular PSA and did not affect levels of the androgen receptor. In androgen-unresponsive prostate cancer cells, YZ had a much less pronounced suppressive effect on proliferation of PC-3 and DU-145 cells, compared to LNCaP, and was inactive against JCA-1 cells. Western blot analyses show that the expression of Rb, a key regulatory protein in G1/S transition, and PCNA, integrally involved in mammalian cell DNA replication, were significantly reduced by treatment with YZ in PC-3 and DU-145 cells, respectively. In contradiction, none of these biochemical parameters were affected in JCA-1 cells under identical treatment conditions. Further analysis shows that YZ increased the levels of signal transducer and activator family of transcription factors STAT 1 and STAT 3 in JCA-1 and not LNCaP cells. The greater sensitivity of LNCaP cells to this polysaccharopeptide raises the possibility that YZ may be considered as an adjuvant therapy in the treatment of hormone responsive prostate cancer; additionally, it may have chemopreventive potential to restrict prostate tumorigenic progression from the hormone-dependent to the hormone-refractory state.
XW Mao, LM Green, DS Gridley.
Department of Radiation Medicine (Radiobiology Program), Loma Linda University and Medical Center, Loma Linda, Calif. 92354, USA. email@example.com
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.
LC Song, HS Chen, N Lou, C Song, J Zeng, TH Fu.
Laboratory for Molecular Pharmacology, Department of Hygiology, First Military Medical University, Guangzhou 510515, China. firstname.lastname@example.org
AIM: To investigate the effect of Coriolus versicolor polysaccharide B (CVPS-B), a new water-soluble component of polysaccharides from the fungus Coriolus versicolor (Fr) L on monocyte chemoattractant protein-1 (MCP-1) gene expression in rat splenocytes. METHODS: Expression of MCP-1 mRNA in rat splenocytes was examined by reverse transcription-polymerase chain reaction (RT-PCR) with beta- actin as an internal standard. Sequencing of RT-PCR products was performed to confirm their specificity in MCP-1 gene composition. RESULTS: (1) Without pre-treatment of lipopolysaccharide (LPS), the relative MCP-1 mRNA expression ratios (MCP-1/beta-actin) for the saline control group and for CVPS-B groups in 3 different doses (10, 20, and 30 mg . kg-1 . d-1, ip, for 4 d) were 1.4 +/- 0.3, 1.6 +/- 0.4, 1.7 +/- 0.5, and 1.5 +/- 0.4, respectively (P > 0.05); (2) LPS (10 microg . kg-1, ip) enhanced the expression of MPC-1 mRNA by the ratio of 114 %; (3) pre-treatment with CVPS-B of 4 different doses (5, 10, 30, and 50 mg . kg-1 . d-1, ip, for 4 d) decreased the LPS induced expression of MPC-1 mRNA by the ratios of 51 %, 70 %, 84 %, and 99 %, respectively (n = 6). CONCLUSION: In a dose-related fashion, CVPS-B inhibited the expression of MCP-1 mRNA induced by LPS in the rat splenocytes, but did not significantly affect the expression of MPC-1 mRNA in the normal rat.
TC Hsieh, J Kunichki, Z Darzynkiewicz, JM Wu.
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY, USA.
OBJECTIVE: The goal of this in vitro study was to test the cytostatic and cytotoxic activities of extracts derived from the polysaccharopeptide (PSP), I’m-Yunity (Integrated Chinese Medicine Holdings Ltd., Kowloon, Hong Kong) prepared from strain Cov-1 of the mushroom Coriolus versicolor. DESIGN: Different volumes of 70% ethanol and water extracts of I’m-Yunity were incubated with cultures of human promyelocytic leukemic HL-60 cells, and compared to nontreated control cells. At various times after treatment, cells were harvested and analyzed with respect to: (1). proliferation and cell cycle phase distribution, (2). induction of apoptosis, and (3). changes in expression of the immunomodulating cytokines interleukin (IL)-1 beta, IL-6, and IL-8. To test whether extracts also affected normal cells, similar experiments were also performed using isolated peripheral blood lymphocytes from healthy volunteers, with and without stimulation by the mitogen phytohemagglutinin (PHA). The ability of extracts to affect the secretion of IL-1 beta, IL-6, and IL-8 were assessed by enzyme-linked immunosorbent assay. RESULTS: HL-60 cells incubated with various amounts (1, 3, 5, 7.5, and 10 micro l/mL) of the extracts for 1-3 days showed dose-dependent, time-dependent growth suppression and decrease in cell viability. Flow cytometric analysis revealed partial cell arrest in the G(1) phase at less than 5 micro L/mL and induction of apoptosis at 10 micro L/mL or more of ethanol and water extracts, with the latter exhibiting more pronounced inhibition than the former. Experiments performed with lymphocytes demonstrated that extracts of I’m-Yunity alone were without effect; moreover, they also did not affect the lymphocyte response to PHA. Water extract of I’m-Yunity also significantly increased IL-1 beta and IL-6 while substantially lowering IL-8. CONCLUSIONS: I’m-Yunity acts selectively in HL-60 leukemic cells, resulting in cell cycle restriction through the G(1)/S checkpoint and the induction of apoptosis.
JL Mau, HC Lin, CC Chen.
Department of Food Science, National Chung-Hsing University, 250 Kuokuang Road, Taichung 402, Taiwan, Republic of China. email@example.com
Three species of medicinal mushrooms are commercially available in Taiwan, namely, Ganoderma lucidum (Ling-chih), Ganoderma tsugae (Sung-shan-ling-chih), and Coriolus versicolor (Yun-chih). Methanolic extracts were prepared from these medicinal mushrooms and their antioxidant properties studied. At 0.6 mg/mL, G. lucidum, G. lucidum antler, and G. tsugae showed an excellent antioxidant activity (2.30-6.41% of lipid peroxidation), whereas C. versicolor showed only 58.56%. At 4 mg/mL, reducing powers were in the order G. tsugae (2.38) approximately G. lucidum antler (2.28) > G. lucidum (1.62) > C. versicolor (0.79). At 0.64 mg/mL, scavenging effects on the 1,1-diphenyl-2-picrylhydrazyl radical were 67.6-74.4% for Ganoderma and 24.6% for C. versicolor. The scavenging effect of methanolic extracts from G. lucidum and G. lucidum antler on hydroxyl radical was the highest (51.2 and 52.6%) at 16 mg/mL, respectively. At 2.4 mg/mL, chelating effects on ferrous ion were in the order G. lucidum antler (67.7%) > G. lucidum (55.5%) > G. tsugae (44.8%) > C. versicolor (13.2%). Total phenols were the major naturally occurring antioxidant components found in methanolic extracts from medicinal mushrooms. Overall, G. lucidum and G. tsugae were higher in antioxidant activity, reducing power, scavenging and chelating abilities, and total phenol content.
KW Tsang, CL Lam, C Yan, JC Mak, GC Ooi, JC HO, B Lam, R Man, JS Sham, WK Lam.
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China. firstname.lastname@example.org
BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths, and over 60% of patients present with advanced stages. Although polysaccharide peptides (PSP), isolated from the fungus Coriolus versicolor, have been reported to have anti-tumor effects, its clinical efficacy has not been properly evaluated. METHODS: Double-blind placebo-controlled randomized study to evaluate the effects of 28-day administration of PSP (Windsor Pharmaceutical, Hong Kong) on patients, who had completed conventional treatment for advanced NSCLC. RESULTS: Thirty-four patients, with no significant difference in their baseline demographic, clinical or tumor characteristics, or previous treatment regimes (P>0.05) were recruited into each of the PSP and control arms. After 28-day treatment, there was a significant improvement in blood leukocyte and neutrophil counts, serum IgG and IgM, and percent of body fat among the PSP, but not the control, patients (P<0.05). Although the evaluable PSP patients did not improve in NSCLC-related symptoms, there were significantly less PSP patients withdrawn due to disease progression, than their control counterparts (5.9 and 23.5%, respectively; P=0.04; OR 4.00). There was no reported adverse reaction attributable to the trial medications. CONCLUSION: PSP treatment appears to be associated with slower deterioration in patients with advanced NSCLC.
J Cui, Y Chisti.
Institute of Technology and Engineering PN456, Massey University, Private Bag 11 222, 5320, Palmerston North, New Zealand.
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.