Synergistic property of cordycepin in cultivated Cordyceps militaris-mediated apoptosis in human leukemia cells.
Cordyceps militaris is a well-known Chinese traditional medicinal mushroom frequently used for tonics and recently of a potential interest for cancer intervention. Here, we explored the cancer cell killing activity of the hot water extracts of C. militaris cultured mycelia ([CM.sub.MY]) and cultivated fruiting bodies ([CM.sub.FB]). We found that [CM.sub.FB] exhibited a greater cytotoxic effect against various cancer cells over [CM.sub.MY]. Apoptotic phenotypes including apoptotic body formation, DNA laddering, caspase 3 activation and cleavage of PARP proteins were induced by [CM.sub.FB] treatment but only slightly induced by same concentration of [CM.sub.MY] treatment in human HL-60 leukemia cells. Cordycepin in [CM.sub.FB] (10.47 mg/g) is significantly higher (~15.2 times) than that of [CM.sub.MY] (0.69 mg/g). Using isobolographic analysis, the synergy of cytotoxicity was observed across different combined concentrations of [CM.sub.MY] and cordycepin. By complementing cordycepin into [CM.sub.MY] to the level comparable with CMFB, we observed that [CM.sub.MY] (500 [micro]g/ml) with cordycepin (4.8 [micro]g/ml) induced apoptosis to a level similar to that induced by [CM.sub.FB] (500 [micro]g/ml). Together, our results suggest that cordycepin possesses a synergistic cytotoxic effect with Cordyceps militaris-mediated apoptosis in human leukemia cells and therefore explaining a better anti-proliferating activity of [CM.sub.FB] over [CM.sub.MY]
Antrodia camphorata extract induces replicative senescence in superficial TCC, and inhibits the absolute migration capability in invasive bladder carcinoma cells Chiung-Chi Peng a,b,1, Kuan-Chou Chena,c,1, Robert Y. Peng a,d, Charng-Cherng Chyaud, Ching-Hua Sua,e, Hsiu Mei Hsieh-Li a,f,∗
a Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Xing Street, Taipei 110, Taiwan b Department of Nursing, Cardinal Tien College of Nursing, No. 364, Chung Cheng Road, Hsintien City, Taipei Hsien 23148, Taiwan c Department of Urology, Taipei Medical University Hospital, Taipei Medical University, 250 Wu-Xing Street, Taipei 110, Taiwan d Research Institute of Medicinal Science and Technology, Hung-Kuang University, No. 34, Chun-Chie Road, Shalu City, Taichung Hsien 43302, Taiwan e Graduate Institute of Biomedical Material, Taipei Medical University, No. 250, Wu-Xing Street, Taipei 110, Taiwan f Department of Life Science, National Taiwan Normal University, 88, Sec. 4, Ting-Chou Road, Taipei 116, Taiwan
Abstract The Antrodia camphorata crude extract (ACCE), an extract obtained from a precious traditional Chinese folkloric herbal medicine Zhan-Ku (a camphor tree mushroom) since the 18th century, has showed rather significant inhibitory effects on the growth and proliferation of the transitional cell carcinomas (TCC) cell lines RT4, TSGH-8301, and T24. On treatment with ACCE at 100 g/mL, the p53-independent overexpression of p21 with simultaneous down alteration of pRbwas observed inRT4, whichwas thus speculative of proceeding through a mechanism of replicative senescence. On the contrary treatment with ACCE, at 50 g/mL, resulting in simultaneous down-regulations of Cdc2 and Cyclin B1, with suppression of the absolute migrating capability of the two cell lines TSGH-8301 and T24, and eventually the cell deaths. We conclude that ACCE can be rather effective and beneficial in suppression of both the superficial cancer cell line RT4 and the metastatic cell lines (TSGH-8301 and T24) through different mechanisms.
Inhibition of Anchorage-Independent Proliferation and G0/G1 Cell-Cycle Regulation in Human Colorectal Carcinoma Cells by 4,7-Dimethoxy-5-Methyl-l,3-Benzodioxole Isolated from the Fruiting Body of Antrodia camphorate
1Department of Chemistry, Tunghai University, Taichung, Taiwan 2Graduate Institute of Biomedical Technology, Taipei Medical University, Taipei 110, Taiwan 3Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan 4Graduate Institute of Neuroscience, Taipei Medical University, Taipei, Taiwan 5Department of Applied Chemistry, Chung Shan Medical University, Taichung 402, Taiwan
In this study, 4,7-dimethoxy-5-methyl-l,3-benzodioxole (SY-1) was isolated from three different sources of dried fruiting bodies of Antrodia camphorate (AC). AC is a medicinal mushroom that grows on the inner heartwood wall of Cinnamomum kanehirai Hay (Lauraceae), an endemic species that is used in Chinese medicine for its anti-tumor and immunomodulatory properties. In this study, we demonstrated that SY-1 profoundly decreased the proliferation of human colon cancer cells (COLO 205) through G0/G1 cell-cycle arrest (50–150 μM) and induction of apoptosis (>150 μM). Cell-cycle arrest induced by SY-1 was associated with a significant increase in levels of p53, p21/Cip1 and p27/Kip1, and a decrease in cyclins D1, D3 and A. In contrast, SY-1 treatment did not induce significant changes in G0/G1 phase cell-cycle regulatory proteins in normal human colonic epithelial cells (FHC). The cells were cultured in soft agar to evaluate anchorage-independent colony formation, and we found that the number of transformed colonies was significantly reduced in the SY-1-treated COLO 205 cells. These findings demonstrate for the first time that SY-1 inhibits human colon cancer cell proliferation through inhibition of cell growth and anchorage-independent colony formation in soft agar. However, the detailed mechanisms of these processes remain unclear and will require further investigation.
Source : Evidence-Based Complementary and Alternative Medicine Volume 2011 (2011), Article ID 984027, 10 pages doi:10.1093/ecam/nep020 Link to Full Article
Phase I Clinical Study of the Dietary Supplement, Agaricus blazei Murill, in Cancer Patients in Remission Satoshi Ohno,1,2 Yoshiteru Sumiyoshi,3,4 Katsuyoshi Hashine,4 Akitomi Shirato,4 Satoru Kyo,2 and Masaki Inoue2
1Consolidated Research Institute for Advanced Science and Medical Care, Waseda University (ASMeW), 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, Japan 2Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan 3Department of Urology, Gengendo Kisarazu Clinic, 4737 Takayanagi, Kisarazu, Chiba 292-0014, Japan 4Department of Urology, Shikoku Cancer Center, 160 Ko, Minamiumemoto-machi, Matsuyama, Ehime 791-0280, Japan
Abstract Although many cancer patients use complementary and alternative medicine, including Agaricus blazei Murill (ABM), safety is not yet well understood. Cancer survivors took 1.8, 3.6, or 5.4 g ABM granulated powder (Kyowa Wellness Co., Ltd., Tokyo, Japan) per day orally for 6 months. Adverse events were defined by subjective/objective symptoms and laboratory data according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTCAE v3.0). Seventy-eight patients were assessed for safety of ABM (30/24/24 subjects at 1/2/3 packs per day, resp.). Adverse events were observed in 9 patients (12%). Most were digestive in nature such as nausea and diarrhea, and one patient developed a liver dysfunction-related food allergy, drug lymphocyte product. However, none of these adverse events occurred in a dose-dependent manner. This study shows that ABM does not cause problems in most patients within laboratory parameters at the dosages tested over 6 months. This trial supports previous evidence that the ABM product is generally safe, excluding possible allergic reaction.
.....In Japan, researchers have demonstrated antioxidant, antimutagenic, antitumor, cancer inhibitory, cancer preventive and immunoenhancing effects of Agaricus blazei Murill experimentally [3–12].
Source : Evidence-Based Complementary and Alternative Medicine Volume 2011 (2011), Article ID 192381, 9 pages doi:10.1155/2011/192381 Link to Full Article
First isolation and characterization of a novel lectin with potent antitumor activity from a Russula mushroom. Zhang G, Sun J, Wang H, Ng TB.
State Key Laboratory for Agrobiotechnology and Department of Microbiology, China Agricultural University, Beijing 100193, China.
To date only a ribonuclease and a protein with anti-HIV-1 reverse transcriptase activity have been isolated from mushrooms of the genus Russula. In this study a novel lectin, with a molecular weight of 32 kDa, and a unique N-terminal sequence different from other lectins, was isolated from the mushroom Russula lepida. It represents the first lectin isolated from Russula mushrooms. The purification scheme involved [([NH.sub.4]).sub.2][SO.sub.4] precipitation, ion exchange chromatography on diethylaminoethyl DEAE-cellulose and SP-Sepharose, and fast protein liquid chromatography-gel filtration on Superdex 75. The hemagglutinating activity of the lectin (RLL) was inhibited by inulin and O-nitrophenyl-[beta]-D-galacto-pyranoside. The lectin was stable at temperatures up to 70 [degrees]C (half of the activity was preserved at 80 [degrees]C), and in the presence of NaOH or HC1 solutions up to a concentration of 12.5 mM. Its hemagglutinating activity was reduced in the presence of [Mn.sup.2+], [Co.sup.2+], and [Hg.sup.2+] ions, and enhanced by [Cu.sup.2+] ions. It exhibited antiproliferative activity toward hepatoma Hep G2 cells and human breast cancer MCF-7 cells with an [IC.sub.50] of 1.6 [micro]M and 0.9 [micro]M, respectively. Daily intraperitoneal injections of RLL (5.0 mg/kg body weight/day for 20 days) brought about 67.6% reduction in the weight of S-180 tumor. RLL was devoid of antifungal, ribonuclease, and HIV-1 reverse transcriptase inhibitory activities.
,,,,,In summary, a lectin with a distinctive N-terminal sequence, sugar specificity, hemagglutinating activity with relatively high thermostability and [Cu.sup.2+] -induced enhancement, and potent antiproliferative and antitumor activities was isolated from R. lepida fruiting bodies. The potent antitumor activity of RLL is remarkable and hopefully it can be developed into an agent for cancer therapy. This report represents an addition to the existing list of mushroom lectins.
Anti-cancer Effects of Protein Extracts from Calvatia lilacina, Pleurotus ostreatus and Volvariella volvaceaJin-Yi Wu1, Chi-Hung Chen2, Wen-Huei Chang3, King-Thom Chung4, Yi-Wen Liu1, Fung-Jou Lu5 and Ching-Hsein Chen1,*
1Graduate Institute of Biomedical and Biopharmaceutical Sciences, College of Life Sciences, 2Graduate Institute of Food Science and Biopharmaceutics, National Chiayi University, Chiayi, 3Department of Chemical Biology, National Pingtung University of Education, Pingtung, Taiwan, 4Department of Biology, The University of Memphis, Memphis, TN, USA and 5Department of Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan
Calvatia lilacina (CL), Pleurotus ostreatus (PO) and Volvariella volvacea (VV) are widely distributed worldwide and commonly eaten as mushrooms. In this study, cell viabilities were evaluated for a human colorectal adenocarcinoma cell line (SW480 cells)and a human monocytic leukemia cell line (THP-1 cells). Apoptotic mechanisms induced by the protein extracts of PO and VV were evaluated for SW480 cells. The viabilities of THP-1 and SW480cells decreased in a concentration-dependent manner after 24h of treatment with the protein extracts of CL, PO or VV. Apoptosis analysis revealed that the percentage of SW480 cells in theSubG1 phase (a marker of apoptosis) was increased upon PO andVV protein-extract treatments, indicating that oligonucleosomal DNA fragmentation existed concomitantly with cellular death.The PO and VV protein extracts induced reactive oxygen species(ROS) production, glutathione (GSH) depletion and mitochondrial transmembrane potential (m) loss in SW480 cells. Pretreatment with N-acetylcysteine, GSH or cyclosporine A partially prevented the apoptosis induced by PO protein extracts, but not that induced by VV extracts, in SW480 cells. The protein extracts of CL,PO and VV exhibited therapeutic efficacy against human colorectal adenocarcinoma cells and human monocytic leukemia cells. The PO protein extracts induced apoptosis in SW480 cells partially through ROS production, GSH depletion and mitochondrial dysfunction.Therefore, the protein extracts of these mushrooms could be considered an important source of new anti-cancer drugs.
Source: eCAM Advance Access published online on May 18, 2010 eCAM, doi:10.1093/ecam/neq05 LINK TO FULL ARTICLE
Role of Ganoderma Supplementation in Cancer Management
Raymond Y Chang. Meridian Medical Group at the Institute of East-West Medicine and Department of Medicine, Cornell Medical College ABSTRACT Ganoderma has been used as folk medicine since ancient times and it is a popular health food frequently promoted as a cancer cure. It is now well established from in vitro and animal studies that the polysaccharide fraction of Ganoderma is largely responsible for its antitumor efficacy. Although there is yet no controlled clinical trials in humans for Ganoderma against cancer to date, the indications for its supplemental use can be indirectly supported with clinical trial data from comparable fungal polysaccharides because of a common final pathway of action mediated via the beta-glucan receptor. Based on such indirect data, indications for Ganoderma use in cancer include supplementation a) to reduce side-effects during chemotherapy or radiotherapy, b) to prolonging survival and minimize metastasis, c) to improve quality of life, and d) to prevent occurrence or recurrence. In sum, although the cure of any cancer with Ganoderma alone is unlikely, it is probably beneficial under defined circumstances in most cases of malignancy.
Ulrike Lindequist*, Timo H. J. Niedermeyer and Wolf-Dieter Jülich Institute of Pharmacy, Ernst-Moritz-Arndt-University Friedrich-Ludwig-Jahn-Strasse 17, 17487 Greifswald, Germany
This review describes pharmacologically active compounds from mushrooms. Compounds and complex substances with antimicrobial,antiviral, antitumor, antiallergic, immunomodulating, anti-inflammatory,antiatherogenic, hypoglycemic, hepatoprotective and central activities are covered, focusing on the review of recent literature.The production of mushrooms or mushroom compounds is discussed briefly.
........Tumor diseases are one of the main causes of death worldwide.Experience from Asian and Eastern Europe countries shows that mushrooms could play an important role in prevention and treatment of cancer Piptoporus betulinus (Bull.: Fr.) P. Karst. was used traditionally in Bohemia for the treatment of rectal cancer and stomach diseases It is also known as fungus of the‘iceman’ from the Copper Age found in 1991, who carried P. betulinus fruiting bodies attached to his clothing on his journey in the Alps. Eastern Europe, the fruiting bodies of I. obliquus have been used as a folk medicine for cancer and stomach diseases since the 16th or 17th century. Antitumor effects of several extracts and isolated compounds could be demonstrated in tumor cell systems and in animal assays. Several triterpenes and ergosterol peroxide contribute to the activity. The melanin complex of I. obliquus has high antioxidant and genoprotective effects on peroxidase-catalyzed oxidation of aminodiphenyls
So called ‘immunomodulators’ (biological response modifier, immunopotentiators and immunostimulants) are the most important medicinal mushroom drugs used especially in Japan,China, Korea and other East Asian countries today. They are summarized in the following sections.