The Role of Medicinal Mushrooms in Cancer Therapy

The Role of Medicinal Mushrooms in
Cancer Therapy
Martin Powell
BSIO Meeting, London – 29/09/14
SHEN NONG BEN CAO
2nd Century AD
• Fu Ling (Poria cocos)
• Yun Zhi (Coriolus versicolor)
• Ling Zhi (Ganoderma lucidum Reishi)
• Bai Mu Er (Tremella fuciformis Snow Fungus).
All classified as Superior Herbs, defined as having excellent
therapeutic action, few or no side effects, may safely be
taken for long periods and of which it is said that ‘prolonged
use will lighten the body and confer longevity’!
• In a 15 year study of 174,505 inhabitants of the Nagano area of Japan,
mushroom farmers were found to have a much lower rate of death
from cancer than the general population (97.1/100,000 cf.
160.1/100,000).1
• An epidemiological study of 2,000 Chinese women, half with breast
cancer and half without, found a reduction in risk of breast cancer in
those women who regularly consumed mushrooms (10g/day fresh or
4g/day dried) and drank green tea (1.05g/day dried green tea leaves)
with an increased reduction in women who did both. 2
• Two Korean studies comparing women with histologically confirmed
breast cancer and an equal number of women without breast cancer
also found a strong inverse correlation between mushroom
consumption and breast cancer risk. 3
1. Zhang M, Huang J, Xie X, Holman CD. Dietary intakes of mushrooms and green tea combine to reduce the risk of breast
cancer in Chinese women. Int J Cancer. 2009 Mar 15;124(6):1404-8.
2. Ikekawa T. Cancer Risk Reduction by Intake of Medicinal Mushrooms. Int J Med Mush. 2005;7(3):347
3. Hong SA, Kim K, Nam SJ, Kong G, Kim MK. A case-control study on the dietary intake of mushrooms and breast cancer
risk among Korean women. Int J Cancer 2008;122(4):919-23
Mushroom-derived anti-cancer agents
licensed in Japan
KRESTIN / PSK
(oral)
LENTINAN
(injection)
SIZOFRAN / SPG
(injection)
Trametes versicolor
(Coriolus) mycelium
Lentinula edodes
(Shiitake) fruiting
body
Schizophyllan commune
culture medium
May 1977
Dec 1985
Apr 1986
Digestive, lung and
breast cancer
Stomach cancer
Cervical cancer
PSK CLINICAL TRIALS – STOMACH CANCER
Stomach Cancer
Stage IV
Kaibara et al, 1976
Surgery w/MMC
+/- PSK w/chemo
66
PSK w/chemo doubled 2yr survival
Advanced Stomach
Cancer with
Metastases
Kodama et al, 1982
Surgery w/MMC
+/- PSK w/chemo
450
PSK w/chemo doubled 5yr survival
Stomach Cancer
Stage III – DOUBLE
BLIND
Kondo and Torisu, 1985
Surgery/no chemo +/PSK
144
PSK extended diseasefree period and enhanced
immunity
Advanced Stomach
Cancer with
Metastases
Maehara et al. 1990
Surgery + MMC + chemo
+/- PSK
255
PSK w/chemo extended
15-yr survival
Stomach Cancer IIV
Nakazato et al,1994
Surgery +chemo +/-PSK
253
PSK extended 5-yr
survival and disease-free
period
Kidd P. The use of mushroom glucans and proteoglycans in cancer treatment. Alternative Medicine Review: A Journal of Clinical
Therapeutic 2000; 5:4–27
PSK CLINICAL TRIALS – OTHER CANCERS
Colorectal Cancer
DOUBLE BLIND
Kondo and Torisu, 1990
Surgery/no chemo +/PSK
110
PSK extended 8-yr
survival and disease-free
period
Oesophageal
Ogoshi et al, 1995
Surgery + radio. +/chemo. +/- PSK
158
PSK extended 5-yr post
surgery+RT+CT and
normalised serum factors
Lung (NSCLC)
Stages I-III
Hayakawa et al, 1993
Radiotherapy +/- PSK
185
PSK extended 5-yr
survival 2-4x all stages.
<5cm >70yr max benefit
Breast, ER+/- Stage
II, post-surgery
Toi et al. 1992
MMC +/- Tamoxifen +/Ftorafur +/- PSK
914
PSK extended survival in
ER-neg, non-metastasized
Breast Stages I, II
Iino et al, 1995
FEMP chemotherapy +
Levamisole or PSK
227
PSK trend to extend 10-yr
survival + disease-free
period. HLA B40+ 100%
• In a systematic review and meta-analysis aggregating and analyzing the
efficacy of Coriolus exracts on survival of cancer patients from 13
randomized, placebo-controlled clinical trials, Coriolus was found to
result in a significant survival advantage compared with standard
conventional anti-cancer treatment alone.
• Of patients randomized to Coriolus, there was a 9% absolute reduction
in 5-year mortality, resulting in one additional patient alive for every 11
patients treated. In patients with breast cancer, gastric cancer, or
colorectal cancer treated with chemotherapy, the effects of the
combination of Coriolus preparation on the overall 5-year survival rate
was more evident, but not in esophageal cancer and nasophayngeal
carcinoma.
• Subgroup analysis could not conclude which type of anti-cancer
treatment may maximize the benefit from Coriolus.
Eliza WL, Fai CK, Chung LP. Efficacy of Yun Zhi (Coriolus versicolor) on survival
in cancer patients: systematic review and meta-analysis. Recent Pat Inflamm
Allergy Drug Discov. 2012 Jan;6(1):78-87.
MD Anderson Cancer Centre’s Detailed Scientific
Review of Coriolus
• ‘Coriolus is a promising candidate for chemoprevention due to the
multiple effects on the malignant process, limited side effects and
safety of daily oral doses for extended periods of time.’
• PSK and PSP seem to work at multiple steps of the malignant
process by inhibiting adhesion, invasion, motility, and metastatic
growth of tumor cells in animal models of cancer.
• Adhesion and invasion are inhibited by suppression of cell matrixdegrading enzyme production by malignant cells.
• Motility of malignant cells and subsequent attachment to blood
vessels are inhibited by suppression of tumor-cell induced platelet
aggregation and anti-angiogenic factors.
http://www.coriolusversicolor.us/wp-content/uploads/2010/09/coriolus-versicolor-medical-trials4001.pdf
• Immune responsiveness of the host does not appear to be affected by
PSK under normal conditions, but immune systems depressed by
tumor-burden or chemotherapy, have reportedly been restored to
normal levels by PSK in animal studies.
• Immune restoration has included antibody and cytokine production and
improvement of impaired antitumor activity of natural killer cells, T
cells, macrophages and peripheral blood lymphocytes in vivo and in
vitro.
• PSK has also been demonstrated to inhibit the decline of
immunocompetence during the perioperative period and inhibit the
growth of residual tumors following cryoablation.
• PSP has also been shown to reverse tumor-induced immunodeficiencies
in sarcoma-bearing mice by increasing immunoglobulin G and C3
complement levels. It has also been associated with increases in white
blood cell count, CD4, CD8, B-lymphocytes, and neutrophils, along with
a higher survival rate of tumor bearing mice.
Toxicology of PSK
• PSK has been associated with side effects of gastrointestinal upset and
darkening of the fingernails, but these effects have been limited and
general safety has been demonstrated with daily oral doses for
extended periods of time. It does not seem to interact with hepatic
drug-metabolizing enzymes involved in the chemical processing of
most chemotherapy agents, and no genetic damage has been detected
by the Ames test.
• At doses that produced necrotic changes in tumor cells, PSP produced
no lesions in the vital organs of tumor-bearing mice after treatment for
two months. It has not been associated with teratogenic effects in mice
or rats.
• 1994 Gastric cancer trial by the Nakazato and Koike of the Study Group
for Immuno-chemotherapy reported in the Lancet (1994;343:11221126) concluded that no toxic effects could be observed from PSK
“even after meticulous review of all the patient records”.
Lentinan
From Lentinula edodes
(Shiitake)
Meta-analysis of 5 clinical trials with a total of 650
participants showed that the addition of lentinan at
2mg/week to standard chemotherapy offers a significant
advantage over chemotherapy alone in terms of survival
for patients with advanced gastric cancer, with patients
with lymph node metastasis having slightly better results
than those with non-lymph node metastasis . 1
1. Individual patient based meta-analysis of lentinan for unresectable/recurrent gastric cancer. Oba K, Kobayashi
M, Matsui T, Kodera Y, Sakamoto J. Anticancer Res. 2009 Jul;29(7):2739-45.
• Additional trials confirm increased survival, reduced side
effects from chemotherapy and improved quality of life in
patients with colorectal, hepatocellular, breast cancer and
metastatic prostate cancer. In a trial with 69 patients with
metastatic prostate cancer the 50% survival length of
treated and control patients was 48 and 35 months,
respectively while the the five-year survival rate of treated
patients was 43% against 29% in the control group1,2.
• Although usually delivered by injection, Lentinan is also
orally bioavailable although the clinical dosage is likely to be
significantly higher 3,4.
1. [Effects of lentinan in advanced or recurrent cases of gastric, colorectal, and breast cancer]. Taguchi T.
Gan To Kagaku Ryoho. 1983 Feb;10(2 Pt 2):387-93. [Article in Japanese]
2. [Effect of lentinan for advanced prostate carcinoma]. Tari K, Satake I, Nakagomi K, Ozawa K, Oowada F,
Higashi Y, Negishi T, Yamada T, Saito H, Yoshida K. Hinyokika Kiyo. 1994 Feb;40(2):119-23.
3. Inhibition of human colon carcinoma development by lentinan from shiitake mushrooms (Lentinus
edodes). Ng ML, Yap AT. J Altern Complement Med. 2002 Oct;8(5):581-9.
4. The Medicinal Benefits of Lentinan (β-1, 3-D glucan) from Lentinus edodes (Berk.) Singer (Shiitake
Mushroom) Through Oral Administration. Yap AT, Ng MH. Int J Med Mushr. v7.i12.170
Grifola frondosa
Maitake
Hen of the Woods
D-fraction / MD-fraction
In a non-randomised study of 165 patients with stage III-IV
cancer given Maitake D-fraction with Maitake fruiting body
tumour regression and/or significant symptomatic
improvement was seen in 66% of lung cancer patients, 54%
of liver cancer patients, 56% of pancreatic cancer patients
and 74% of breast cancer patients1.
1. Anti tumor activity of orally administered d-fraction from Maitake (Grifola frondosa). Nanba H. J
Naturopathic Medicine. 1993 1:10-15
• In a separate study a combination of MD-fraction and
whole Maitake fruiting body powder was reported to
produce similar improvements: 58.3% of liver cancer
patients, 68.8% of breast cancer patients and 62.5% of
lung cancer patients1.
• In vivo studies also showed synergy between D-fraction
and chemotherapy (mitomycin C) as well as significant
alleviation of side effects from chemotherapy, including
loss of appetite, vomiting, nausea, hair loss and
leukopenia2.
1. Can Maitake MD-Fraction Aid Cancer Patients? Kodama N, Komuta K, Nanba H. Alt Med Rev. v.7,3. 2002
2. Maitake extracts and their therapeutic potential - A Review. Mayell M. Alt Med Rev, v.6.1. 2001
Agaricus subrufescens
(Agaricus blazei / brasiliensis)
Almond Mushroom
• A. blazei polysaccharide extracts show strong in-vitro and in-vivo activity
against a range of cancer cell lines, including: lung and ovarian cancer1.
• Clinical studies are limited although Mizuno reports positive clinical
results in a number of mainly breast cancer patients at unspecified
dosage while Ahn reports increased NK-cell activity and reduced
chemotherapy related side effects from A. blazei polysaccharide
extract2.
• A 2008 study confirms increases in NK cell activity with A. blazei
polysaccharide extract a dose of 3g/day3.
1. Antitumor beta-glucan from the cultured fruit body of Agaricus blazei. N. Ohno, M. Furukawa and N. Miura. Biol. Pharm. Bull. 24 (2001),
pp. 820–828.
2. Medicinal properties and clinical effects of culinary-medicinal mushroom Agaricus blazei Murrill (Agaricomycetideae) (Review). T.
Mizuno. Int. J. Med. Mushr. 4 (2002), pp. 299–312.
3. Immunomodulating Activity of Agaricus brasiliensis KA21 in Mice and in Human Volunteers. Liu Y, Fukuwatari Y, Okumura K, Takeda K,
Ishibashi KI, Furukawa M, Ohno N, Mori K, Gao M, Motoi M. Evid Based Complement Alternat Med. 2008 Jun;5(2):205-219.
1-3, 1-6-Beta Glucan
Lentinan - a polysaccharide isolated from Shiitake
and licensed in Japan as a pharmaceutical drug.
Heteropolysaccharides – as well as Glucose mushroom polysaccharides
typically contain other sugars, such as Mannose, Galactose, Xylose, Fucose,
e.g.:
• Xylogalactoglucan – Inonotus obliquus (Chaga)
• Glucomannan – Agaricus blazei
• Galactoglucomannan – Lentinus edodes (Shiitake)
• Mannogalactofucan – Grifola frondosa (Maitake)
• Galactoxyloglucan – Hericium erinaceous (Lion’s Mane)
• Glucoronoxylomannans – Tremella fuciformis (Snow Fungus)
Although most research has focussed on β Glucans, especially β-1,3 and β-1,4
linked, α-1,4 and α-1,6 glucans have also shown anti-tumour activity
It also
that the most active polysaccharide fractions have bound
• appears
protein components (proteoglycans).
Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. S.P.
Wasser. Appl Microbiol Biotechnol (2002) 60:258-274
PSK (Krestin) and PSP from Trametes versicolor
• PSK is a a purified hot-water extract consisting of proteinbound polysaccharide molecules with an average
molecular weight of 94kDa.
• Protein component ranges from 25-38%.
• The main constituent monosaccharide is glucose wıth
small amounts of other sugar residues, such as mannose,
fucose, xylose and galactose. The main chain consists of
beta 1-4 linked units with side chains of beta 1-3 as well as
beta 1-6 linked glucose residues.
• PSP is similar to PSK but differs in the presence of
rhamnose and arabinose.
Renn L, Prera C, Hemar Y. Antıtumor actıvıty of mushroom polysaccharıdes:a revıew. Food Funct. 2012;3:1118-1130.
Immune changes induced by mushroom
polysaccharide-based supplementation
include:
• Increased NK cell activation
• Increased macrophage activation
• Increased cytotoxic T-cell activation
• Increased IFN-γ, IL-2 and TNF-β production
• Reduced IL-4 production
• Inhibition of prostaglandin synthesis
TH1
TH2
Cellular Immunity / Cytotoxic
Humoral (Antibody mediated)
Immunity / Pro-inflammatory
Interferon-γ and TNF-β
IL-4, IL-5, IL-6, IL-13
High NK cell activity and classical
(antimicrobial) macrophage activation
Low NK cell activity and alternative
(proliferative and collagen producing)
macrophage activation
Infectious diseases
Chronic inflammatory conditions
Factors promoting the development of
Th1 and Th2 phenotypes
TH1
TH2
Presence of older siblings
Stress / Cortisol
Early exposure to day care
Chemical and heavy metal exposure
Infectious diseases in childhood
Multiple vaccinations
Mikael Häggström - Rang, H. P. (2003) Pharmacology, Edinburgh: Churchill Livingstone Page 223
Consequences of a TH1 - TH2 Shift
• Lowered resistance to viral and other pathogens.
• Increases in fatigue and incidence of depression.
• Increases incidence of allergic and auto-immune conditions
such as asthma and SLE.
• Persistent humoral immune responses exacerbate
recruitment and activation of innate immune cells in
neoplastic microenvironments where they regulate tissue
remodelling, pro-angiogenic and pro-survival pathways that
together potentiate cancer development.1
1. Tan TT, Coussens LM. Humoral immunity, inflammation and cancer. Curr Opin Immunol. 2007 Apr;19(2):209-16
Dectin-1
• Commonly expressed in macrophages, neutrophil lineages,
dendritic cells and some T-cells but not NK-cells.
• Considered the most important receptor for the activation
of the innate immune response in macrophages.
• Binds specifically to β-(1→3)-glucans but only those
consisting of at least 10 monomers
• Binding activates phagocytosis, ROS production and
induction of TNF-α, IL-2, IL-10, IL-12
Medicinal Importance of fungal β- (1→3), (1→6)-glucans. Jiezhong Chen, Robert Seviour. Mycological Research
III (2007). 635-652
CR3
• Expressed mainly on Neutrophils, Monocytes and NK
Cells.
• Two binding sites exist on the CD11b domain. One for βglucans and the other for iC3b (cleaved component 3
fragment of serum complement system).
• Binding of β-glucans to CR3 increases adhesion to
microbial cells and activates the iC3b pathway causing
tumour cytotoxicity.
Medicinal Importance of fungal β- (1→3), (1→6)-glucans. Jiezhong Chen, Robert Seviour. Mycological
Research III (2007). 635-652
The effects of β-glucan on human immune and cancer cells. Godfrey Chi-Fung Chan, Wing Keung Chan
and Daniel Man-Yuen Sze. Journal of Hematology & Oncology 2009, 2:25
Mushrooms and Chemotherapy
• Lentinan extended survival and reduced the incidence of
adverse effects in inoperable or recurrent gastric cancer in
conjunction with tegafur as well as S-1-based
chemotherapy (tegafur, gimeracil, oteracil).
• Five-year disease free survival in colorectal cancer cases
was significantly higher with PSK and oral Tegafur/Uracil
(UFT) than with UFT alone (73% vs. 58.8%) and increased
five-year disease-free period (70.7% vs. 59.4%) and
survival (73.0% vs. 60.0%) in gastric cancer when given
together with mitomycin and fluoracil.
• Agaricus subrufescens polysaccharide extract reduced
chemotherapy related side effects (appetite, alopecia,
emotional stability, and general weakness) in 100 cervical,
ovarian, and endometrial cancer patients treated either
with carboplatin plus VP16 (etoposide) or with carboplatin
plus taxol.
• Grifola frondosa polysaccharide fractions potentiated the
action of carmustine and increased efficacy when given in
combination with chemotherapy across a range of cancers,
as well as reducing cisplatin-induced nephrotoxicity.
In addition to supporting the immune system and ameliorating
chemotherapy-induced immune suppression there is some
evidence that mushroom polysaccharide extracts contribute to
the efficacy of the chemotherapeutic drugs themselves through
enhanced production of reactive oxygen species (ROS):
• Liu et al reported an increase in ROS and reactive nitrogen
intermediates in peritoneal macrophages of mice given PSP.
• An extract of A. subrufescens was shown to induce apoptosis
through an ROS-dependent pathway.
• Grifron-D, a polysaccharide extract from G. frondosa, has
been shown to have a direct cytotoxic effect on cancer cells
through oxidative membrane damage leading to apoptosis.
Mushrooms and Radiotherapy
• Reduction in radiation-induced leukopaenia - in a trial with
136 patients undergoing radiotherapy, oral consumption of T.
fuciformis polysaccharide extract (3g/day) resulted in a 13.2%
reduction inWBC compared to a 35.2% reduction in the
control group and T.versicolor mycelial biomass (6g/day)
prevented decreases in red and white blood cells in lung
cancer patients undergoing radiotherapy.
• Enhanced treatment efficacy - oral administration of
T.versicolor extract PSP with radiotherapy significantly
increased the percentage of apoptotic cells at 24hr compared
to radiation alone and reduced radiotherapy induced
reduction in white blood cell count.
Mushrooms’ Prebiotic Activity
Recent research indicates that mushroom polysaccharides
have a prebiotic effect on the gut microbiome with
increases in Bifidobacterium and Lactobacillus species and
decreases in Clostridium, Staphylococcus and Enterococcus
species, together with increased concentration of organic
acids (lactate and short-chain fatty acids), decreased pH
and increased β-galactosidase and β-glucosidase activity
and it has been suggested that this effect may also
contribute to their diverse health benefits1,2.
1. Trametes versicolor extract modifies human fecal microbiota composition in vitro. Yu ZT, Liu B,
Mukherjee P, Newburg DS. Plant Foods Hum Nutr. 2013 Jun;68(2):107-12.
2. Effects of polysaccharopeptide from Trametes Versicolor and amoxicillin on the gut microbiome of
healthy volunteers: A randomized clinical trial. Pallav K. et al. Gut Microbes. 2014 Jul 9;5(4).
CORIOLUS SUPPLEMENTATION FOR LSIL
A 1 year controlled trial using Coriolus versicolor mycelial
biomass in 43 LSIL HPV patients reported results including:
• Cytology returned to normal in 72.5% of patients
receiving Coriolus supplementation (3g/day) compared
to 47.5% in the control group.
• 90% of patients who received supplementation
became –ve for High Risk HPV strains compared to
8.5% in the control group.
Coriolus versicolor supplementation in HPV patients. Couto S. 20th European Congress of
Obstetrics and Gynaecology, 2008.
ACTIVE COMPOUNDS
FROM MEDICINAL
MUSHROOMS
Immunologically
active polysaccharides
Secondary
metabolites
Found in all
mushrooms
Differ from species to
species
Lovastatin
Originally isolated from Penicillium brevicompactum as an antifungal agent (called Compactin), as well as from Penicillium
citrinum and is widespread in mushrooms and other fungi.
Fruiting Body - mg/kg
Porcini
Reishi
Mycelium - mg/kg
131
68
908
Oyster (Korea)
60
Oyster (Taiwan)
147
Golden Oyster
930
Buna-Shimeji
628
Shiitake
316
Agaricus subrufescens
184
Lin SY, Chen YK, Yu HT, Barseghyan GS, Asatiani MD, Wasser SP, Mau JL. Comparative study of contents of several bioactive
components in fruiting bodies and mycelia of culinary-medicinal mushrooms. Int J Med Mushrooms. 2013;15(3):315-23.
Mushrooms’ Anti-Candida Activity
• Mushrooms produce a wide range of anti-fungal
compounds to help them compete with other fungi. 1-3
• Mushrooms help facilitate the immune system’s response
to respond candida. 4-6
• Mushrooms do not contain sugars or starches that could
stimulate the growth of candida.
1. An examination of antibacterial and antifungal properties of constituents of Shiitake (Lentinula edodes) and oyster (Pleurotus ostreatus)
mushrooms. Hearst R, Nelson D, McCollum G, Millar BC, Maeda Y, Goldsmith CE, Rooney PJ, Loughrey A, Rao JR, Moore JE. Complement
Ther Clin Pract. 2009 Feb;15(1):5-7.
2. Antimicrobial properties of shiitake mushrooms (Lentinula edodes). Rao JR, Smyth TJ, Millar BC, Moore JE. Int J Antimicrob Agents. 2009
Jun;33(6):591-2.
3. Antimicrobial and antineoplasic activity of Pleurotus ostreatus. Wolff ER, Wisbeck E, Silveira ML, Gern RM, Pinho MS, Furlan SA. Appl
Biochem Biotechnol. 2008 Dec;151(2-3):402-12.
4. Protective effects of a protein-bound polysaccharide, PSK, on Candida albicans infection in mice via tumor necrosis factor-alpha induction.
Ohmura Y, Matsunaga K, Motokawa I, Sakurai K, Ando T. Int Immunopharmacol. 2001 Sep;1(9-10):1797-811.
5. Paccola E, Maki C, Nobrega G, Paccola-Meirelles L. Antagonistic Effect of Edible Mushroom Extract on Candida Albicans Growth. Braz. J. of
Microbiol. (2001) 32:176-178
6. Polysaccharide-rich fraction of Agaricus brasiliensis enhances the candidacidal activity of murine macrophages. Martins PR, Gameiro MC,
Castoldi L, Romagnoli GG, Lopes FC, Pinto AV, Loyola W, Kaneno R. Mem Inst Oswaldo Cruz. 2008 May;103(3):244-50.
Ling Zhi (Reishi)
Ganoderma lucidum
Ling Zhi – Spirit Mushroom
Mushroom of Immortality
Mannantake – 10,000 Year
Mushroom
Reishi
•
Anti-cancer
•
Anti-inflammatory
•
Anti-histamine
•
Anti-allergic
•
Sedative
•
Anti-hypertensive
•
Antioxidant
•
Hepatoprotective
•
Anti-cholesterol
Cochrane Database Systematic Review of the Use of
Ganoderma Lucidum for Cancer Treatment
• 5 randomised controlled trials met inclusion criteria.
• The meta-analysis results showed that patients who had been given G.
lucidum alongside chemo/radiotherapy were 1.27 times more likely to
respond positively to chemo/radiotherapy compared to those without.
• G. lucidum treatment alone did not demonstrate the same regression
rate as that seen in combined therapy.
• Four studies showed that patients in the reishi group had relatively
improved quality of life in comparison to controls. Only one of the
studies recorded minimal side effects, including nausea and insomnia.
• The results for host immune function indicators suggested that G.
lucidum simultaneously increases the percentage of CD3, CD4 and CD8.
Jin X, Ruiz Bequerie J, Sze DM, Chan GC. Ganoderma lucidum (Reishi mushroom) for cancer treatment.
Cochrane Database Syst Rev. 2012 Jun 13;6:CD007731
Ganoderic and Lucidenic Acids
•
Sedative effect on CNS
•
9 lucidenic acids and 4 ganoderic acids showed strong antiinflammatory activity
•
Inhibit histamine release (Ganoderic Acids A,B,C and D, also
Oleic Acid and Cycooctasulphur)
•
Anti-hepatotoxic (R,S and Ganodosterone)
•
Anti-hypertensive (ACE inhibition - B,D,F,H,K,S,Y)
•
Anti-viral - 11 lucidenic acids and 5 ganoderic acids showed
strong inhibition of EBV. Ganoderma triterpenes also inhibit
HIV-1 protease activity and viral binding and showed potent
inhibitory activity against herpes simplex virus
•
Anti-cancer
Anti-tumour Activity of Ganoderic and Lucidenic Acids
• Suppression of cancer growth and angiogenesis through
modulation of AP-1 and NF-kB signalling
• Induction of apoptosis via a mitochondria-mediated pathway
• Inhibition of cancer cell invasiveness
• Inhibition of aromatase activity
• Suppression of steroid 5α-reductase, which converts
testosterone to dihydrotestosterone (DHT) and has been
shown to play an important role in the development of
prostate cancer and benign prostatic hyperplasia (BPH)
• Enhanced chemosensitivity to cisplatin through inhibition of
the JAK-STAT3 signalling pathway
Anti-cancer properties of triterpenoids isolated from Ganoderma lucidum - a review. Wu GS et al. Expert Opin Investig
Drugs. 2013 Aug;22(8):981-92.
Spore Powder of Ganoderma lucidum Improves
Cancer-Related Fatigue in Breast Cancer
Patients Undergoing Endocrine Therapy: A Pilot
Clinical Trial
• 48 breast cancer patients with cancer-related fatigue
undergoing endocrine therapy with treatment group given
3g/day shell-broken spore powder.
• Significant improvements in physical well-being and fatigue.
• Reductions in anxiety and depression and improved quality
of life.
• Immune markers of CRF were significantly lower.
1. Spore Powder of Ganoderma lucidum Improves Cancer-Related Fatigue in Breast Cancer Patients
Undergoing Endocrine Therapy: A Pilot Clinical Trial. Zhao H, Zhang Q, Zhao L, Huang X, Wang J, Kang X.
Evid Based Complement Alt Med. Epub 2011 Dec 10.
Inonotus obliquus
Chaga – Bai Hua Rong
Widely used as a folk medicine in Russia
and eastern europe to treat cancer and
support the immune system. Credited
with curing Solzhenitzen of cancer.
Contains high levels of betulinic acid
(also one of the key components in
mistletoe) derived from the bark of host
birch trees, with actions including:
•
•
•
•
Anti-retroviral
Anti-malarial
Anti-inflammatory
Anti-cancer
Betulinic Acid and Cancer
• Induces mitochondrial apoptosis in different cancer cell lines
and inhibits the enzyme topoisomerase, which is essential for
the unwinding and winding of the DNA strands in cell
replication.
• In-vitro studies on betulinic acid have shown it to be highly
effective against a wide variety of cancer cells: human
melanoma, neuroectodermal (neuroblastoma,
medulloblastoma, Ewing's sarcoma) and malignant brain
tumors, ovarian carcinoma, human leukemia HL-60 cells and
malignant head and neck squamous cell carcinomas, including
those derived from therapy-resistant and refractory tumors.
Mullauer FB, Kessler JH, Medema JP. Betulinic acid, a natural compound with potent anticancer effects.
Anticancer Drugs. 2010 Mar;21(3):215-27.
• Betulinic acid's action against brain tumor cells is particularly
interesting and it is noteworthy that in one study it exerted
cytotoxic activity against primary tumor cells cultured from
patients in 4 of 4 medulloblastoma-tumor samples tested and
in 20 of 24 glioblastoma-tumor samples.
• It also shows great promise in combination with radiotherapy,
exhibiting a strictly additive mode of growth inhibition in
combination with radiation in human melanoma cells in one
study and acting as a radiosensitizer in head and neck
squamous cell cancers in another.
Mullauer FB, Kessler JH, Medema JP. Betulinic acid, a natural compound with potent anticancer effects.
Anticancer Drugs. 2010 Mar;21(3):215-27.
Cordyceps
Ophiocordyceps sinensis
/ Cordyceps militaris
• Anti-fatigue – Cordyceps has been shown to increase endurance,
efficiency of oxygen utilization and cellular ATP levels. In a trial with 50
asthma patients 81.3% showed improvement with an average of 5 days
using Cordyceps compared to 61.1% taking antihistamines with an
average of 9 days for symptoms to subside.
• Hepato-protective – inhibits hepatic fibrogenesis derived from chronic
liver injury, retards the development of cirrhosis, reduces liver enzyme
levels and significantly improves liver function.
• Anti-cholesterol – decreases plasma cholesterol in rats fed a
cholesterol enriched diet and increases ratio of HDL to LDL.
• Anti-stress – equivalent to ginseng. Counteracted inhibition of weight
gain, increase in adrenal gland weight, increase in glucocorticoid
receptors in the liver, spleen and thymus and increased peroxidation in
the liver and heart.
• Immuno-modulatory and anti-cancer – activates macrophages,
stimulates bone marrow cell proliferation through activation of Peyer’s
patch cells.
Nucleoside Analogues
Cordycepin
Adenosine
3-deoxyadenosine
2,3-dideoxyadenosine
Forerunner of
Didanosine (Videx)
Cordycepin
• Inhibits cancer cell replication1
• Inhibits invasiveness of cancer cells2
• Induces apoptosis of multiple cell lines, including:
• Leukaemia
• Multiple myeloma
• Prostate cancer
• Neuroblastoma
• Oral Cancer
• Anti-inflammatory
1.
2.
Lee HJ, Burger P, Vogel M, Friese K, Brüning A. The nucleoside antagonist cordycepin causes DNA
double strand breaks in breast cancer cells. Invest New Drugs. 2012 Oct;30(5):1917-25
Jeong JW, Jin CY, Park C, Han MH, Kim GY, Moon SK, Kim CG, Jeong YK, Kim WJ, Lee JD, Choi YH.
Inhibition of migration and invasion of LNCaP human prostate carcinoma cells by cordycepin
through inactivation of Akt. Int J Oncol. 2012 May;40(5):1697-704.
Current Issues
• Lack of standardisation
• Different formats:
• Fruiting body
• Mycelium
• Hot-water extracts (polysaccharide-rich)
• Ethanolic extracts (triterpene-rich)
• Mycelial biomass (rich in anti-microbial secondary
metabolites and substrate-breakdown products
such as arabinoxylans but low in beta-glucans and
related polysaccharides)
• Lack of comparative research
• Single mushrooms vs. combinations
[email protected]