Scientific Researches On:
Ganoderma Lucidum (Reishi Mushroom)
USA National Center for Biotechnology Information
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1:
Phytomedicine. 2008 Jan 31. [Epub
ahead of print]
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In vitro cytostatic and
immunomodulatory properties of the
medicinal mushroom Lentinula edodes.
Israilides C,
Kletsas D,
Arapoglou D,
Philippoussis A,
Pratsinis H,
Ebringerová A,
Hříbalová V,
Harding SE.
Biotechnology Laboratory, National
Agricultural Research Foundation (NAGREF),
1, Sof. Venizelou St., 14123 Lycovrissi,
Athens, Greece.
Lentinula edodes, known as "shiitake" is
one of the widely used medicinal mushrooms
in the Orient. Antitumour activity of
extracts of this mushroom has been widely
demonstrated in animals and humans.
However, this activity was shown to be
host mediated and not by direct cytotoxic
activity to cancer cells. This study
demonstrates cytotoxic and cell growth
inhibitory (cytostatic) effect of aqueous
extracts of the mushroom on MCF-7 human
breast adenocarcinoma cell line using an
MTT cytotoxicity assay. Such effect was
demonstrated with fruit body and mycelial
extracts, the difference being that there
was no significant suppression on normal
cells with the latter. Furthermore
mycelial extracts did not induce any
cytostatic effect in both cancer and
normal cell lines based on a DNA synthesis
assay. The significant suppression of the
proliferation of cancer cells was
reflected by the comparatively low IC(50)
values and the simultaneous higher
respective values on normal fibroblast
cells. The immunostimulatory activity of
both fruit body and mycelial extracts was
tested by the lymphocyte transformation
test (LTT), which is based on the capacity
of active immunomodulators to augment the
proliferative response of rat thymocytes
to T mitogens in vitro. Both fruit body
and mycelial preparations were able to
enhance the proliferation of rat
thymocytes directly and act as
co-stimulators in the presence of the T-mitogen
PHA. Interestingly both extracts,
similarly to zymosan showed SI(comit)/SI(mit)
ratios of about 2, indicating adjuvant
properties. Overall L. edodes aqueous
extracts have demonstrated direct
inhibition of the proliferation of human
breast cancer cells in vitro and
immunostimulatory properties in terms of
mitogenic and co-mitogenic activity in
vitro.
PMID: 18242970 [PubMed - as supplied by
publisher]
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A polysaccharide extracted from rice
bran fermented with Lentinus edodes
enhances natural killer cell activity and
exhibits anticancer effects.
Kim HY,
Kim JH,
Yang SB,
Hong SG,
Lee SA,
Hwang SJ,
Shin KS,
Suh HJ,
Park MH.
Erom R&D Center, Erom Co., Ltd., Gyeonggi-do,
Republic of Korea.
The objective of this study was to
investigate the activation of natural
killer (NK) cells and anticancer effects
of exo-biopolymer from rice bran cultured
with Lentinus edodes [rice bran exo-biopolymer
(RBEP)]. Oral administration of RBEP
induced the activation of NK cells in a
dose-dependent manner. RBEP also prolonged
the life spans of mice transplanted with
Sarcoma-180 cells and inhibited growing
Sarcoma-180 cells in intraperitoneum.
Solid tumor growth was also suppressed by
oral administration of RBEP in C57/Bl6
mice transplanted with B16/Bl6 melanoma.
Intraperitoneal injection of RBEP was more
effective than oral administration at the
same dosage in mice with transplanted
tumor cells. According to this result,
when RBEP directly contacts immune cells,
the anticancer activity is higher than by
indirectly inducing an immune response
through oral administration. Therefore, we
suggest that the administration of RBEP
may be effective for preventing and/or
treating cancer through NK cell
activation. However, further studies are
needed to elucidate the possible
mechanisms of the anticancer activity and
to investigate the other beneficial
effects of RBEP for the development of a
new biological response modifier.
PMID: 17472463 [PubMed - indexed for
MEDLINE]
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[Study on effect of lentinan in
enhancing anti-tumor action of dendritic
cytoma vaccine and its mechanism]
[Article in Chinese]
Wang J,
Zhou ZD,
Xia DJ.
Hangzhou Red Cross Hospital, Zhejiang.
OBJECTIVE: To improve the anti-tumor
effect of dendritic cytoma vaccine (DCV)
for finding an effective anti-tumor
biotherapy. METHODS: DC vaccine prepared
by transfection of adenovirus mediated
melanoma-associated antigen gene (gp100)
into bone marrow-derived dendritic cell
(DC) was used to study the immuno-therapeutic
effect and the mechanism of lentinan (LNT)
in different dosages, used alone or
combined with gp100-DC for treatment of
B16 melanoma bearing mice. RESULTS: After
being treated with LNT combining gp100-DC,
the growth of malignant melanoma was
inhibited with the tumor-free survival in
the experimental animals being 66.7%. The
treatment could also significantly enhance
the activity of cytotoxicity T lymphocyte
(CTL) and natural killer (NK) cells,
elevate the levels of interleukin-2 (IL-2)
and interferon-gamma (IFN-gamma) in
splenocytes, and histological examination
showed that a large amount of inflammatory
cells infiltrated inside and around the
tumor, and obvious necrosis of tumor cells
was found. CONCLUSION: By combined use
with LNT the anti-tumor immuno-reaction of
DCV vaccine could be enhanced effectively.
Publication Types:
PMID: 17302067 [PubMed - indexed for
MEDLINE]
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[Anti tumor activities of lentinan and
micellapist in tumor-bearing mice]
[Article in Japanese]
Maruyama S,
Sukekawa Y,
Kaneko Y,
Fujimoto S.
Institute of Immunotherapy for Cancer,
Kinki University.
Although Lentinan (LNT) is sold as a
medicine, and Micellapist (MME) sold as a
food supplement, both LNT and MME are
beta-glucans isolated from the Shiitake
mushroom (Lentinula edodes). These two
substances have been thought to be the
same component of Shiitake. In the present
study, we evaluated anti tumor activities
of LNT and MME in tumor-bearing mice
(B10.D2 mice implanted with S908D2 tumor
cells) and examined the mechanism of
immunopotentiation of these substances.
The tumor growth was significantly
suppressed in the LNT-treated group. In ex
vivo evaluation, the tumor cytotoxicity
was significantly reduced by a treatment
of splenocytes with anti-CD8 antibody in
the LNT-treated group. Furthermore, the
tumor cytotoxicity of the LNT-treated
group was also significantly reduced by a
treatment of splenocytes with anti-CD8
antibody and its complement and with an
anti-CD4 and its complement in the
effector phase and the induction phase,
respectively. A significant prolongation
of the survival of tumor-bearing mice as
compared to the untreated control group
was noted in the LNT-treated group. In the
mice treated intraperitoneally with LNT,
CD8-positive cells appeared to have
suppressed tumor cell proliferation.
CD4-positive cells appeared to be involved
in this activity of CD8-positive cells. On
the other hand, orally administered MME
has exerted no clear cytotoxic effects.
Publication Types:
PMID: 17212088 [PubMed - indexed for
MEDLINE]
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Inhibition of growth and induction of
apoptosis in human cancer cell lines by an
ethyl acetate fraction from shiitake
mushrooms.
Fang N,
Li Q,
Yu S,
Zhang J,
He L,
Ronis MJ,
Badger TM.
Arkansas Children's Nutrition Center,
University of Arkansas for Medical
Sciences, Little Rock, AR 72202, USA.
fangnianbai@uams.edu
OBJECTIVE: Shiitake (Lentinus edodes)
mushrooms have been reported to have
cancer-preventing properties. However,
little research has been conducted
verifying the antitumor activities of "mycochemicals"
in shiitake mushrooms. In this study,
potential roles of an ethyl acetate
fraction from shiitake mushrooms were
investigated by in vitro bioassays.
DESIGN: The activities of an ethyl acetate
fraction were evaluated by
[3-(4,5-dimethylthiazol-yl)-2,5-diphenyltetrazolium
bromide] (MTT), apoptosis bioassay, cell
cycle analysis, and Western blot analysis
using two human breast carcinoma cell
lines (MDA-MB-453 and MCF-7), one human
nonmalignant breast epithelial cell line
(MCF-10F), and two myeloma cell lines
(RPMI-8226 and IM-9). RESULTS:
Concentration-dependent antiproliferative
effects of the fraction were observed in
all cell lines using the MTT assay.
Approximately 50 mg/L concentration of the
fraction induced apoptosis in 50% of the
population of four human tumor cell lines
and the fraction-induced apoptosis may
have been mediated through the
pro-apoptotic bax protein which was
up-regulated. Cell cycle analysis revealed
that the fraction induced cell cycle
arrest by significant decrease of S phase,
which was associated with the induction of
cdk inhibitors p21 and the suppression of
cdk4 and cyclin D1 activity. Compared to
malignant tumor cells, nonmalignant cells
were less sensitive to the fraction for
the suppression of cell growth and
regulation of bax, p21, cyclin D1, and
cdk4 expression. A 51% antiproliferative
effect occurred at the highest
concentration of the fraction (800 mg/L).
CONCLUSIONS: These data suggest that
inhibition of growth in tumor cells by "mycochemicals"
in shiitake mushrooms may result from
induction of apoptosis.
Publication Types:
PMID: 16566671 [PubMed - indexed for
MEDLINE]
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[Antitumor effects of intratumoral
injection of Basidiomycetes preparations]
[Article in Japanese]
Ebina T.
Division of Immunology, Miyagi Cancer
Center Research Institute.
The antitumor effects of Basidiomycetes
preparations in an experimental mouse
model, the "double grafted tumor system"
were analyzed. Some BRMs prevented
metastases by utilizing the anti-tumor
immunological cascade reactions, which
activates macrophages in the body. The
following Basidiomycetes preparations were
analyzed: PSK was a hot water extract of
cultured mycelia from Coliolus versicolor
and a protein bound beta-glucan. Matsumax
was extracted from mycelia of Tricholoma
matsutake and was a protein bound (38%) a-glucan.
The Agaricus preparation was extracted
from fruit bodies of Agaricus blazei and a
protein-bound (17%) a-glucan, beta-glucan.
Himematsutake preparation was extracted
from fruit body of Agaricus blazei (Himematsutake)
and a protein bound (5%) glucan. Lentinan
was purified from fruit bodies of Lentinus
edodes and is a purified beta-glucan. PSK
cured both primary and metastatic tumors
in the double grafted tumor system.
Lentinan inhibited the growth of neither
primary nor metastatic tumors. Matsumax
and Agaricus preparation cured primary
tumor and inhibited the growth of
metastatic tumor. Himematsutake
preparation inhibited the growth of
primary tumor. Immunosuppresive acidic
protein (IAP) is produced by activated
mactrophates. The PSK, Matsumax, Agaricus
preparation and Himematsutake preparation
induced IAP but Lentinan did not.
Publication Types:
PMID: 16315899 [PubMed - indexed for
MEDLINE]
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[Evaluation of host immunity and side
effects in breast cancer patients treated
with adjuvant chemotherapy (FEC therapy)]
[Article in Japanese]
Nagashima Y,
Sanpei N,
Yamamoto S,
Yoshino S,
Tangoku A,
Oka M.
Dept. of Surgery II, Yamaguchi University
School of Medicine.
BACKGROUND: FEC
(5-FU+epirubicin+cyclophosphamide) therapy
has been used as adjuvant chemotherapy for
breast cancer patients with nodes
positive. The aim of this study was to
evaluate host immunity and side effects of
the FEC therapy. The effect of oral
administration of Lentinus edodes mycelia
(LEM) was also observed. METHODS: Ten
patients were enrolled in this study. The
treatment with 5-FU (500 mg/m2),
epirubicin (75 mg/m2) and cyclophosphamide
(500 mg/m2) was administered every 21 days
for 2 cycles, and LEM (9 g/day po) was
administered during the 2nd cycle.
RESULTS: NK cell activity and the number
of white blood cells decreased on the 7th
day after the therapy, and they recovered
on the 21st day. However, this NK cell
activity and the number of white blood
cells didn't decrease when the FEC therapy
was used with LEM po. CONCLUSIONS: FEC 75
therapy has made some impacts on host
immunity, and LEM with the FEC 75 therapy
might have prevented host immunity.
Publication Types:
PMID: 16315865 [PubMed - indexed for
MEDLINE]
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Correlation between antitumor activity,
molecular weight, and conformation of
lentinan.
Zhang L,
Li X,
Xu X,
Zeng F.
Department of Chemistry, Wuhan University,
China. lnzhang@public.wh.hb.cn
A (1-->3)-beta-D-glucan having (1-->6)
branching (L-FV-IB) from Lentinus edodes
in water was degraded into seven fractions
of different molecular weights by
ultrasonic irradiation, and each was
further fractionated into three parts, by
precipitation from water into acetone at
room temperature. The weight-average
molecular weight (M(w)), radius of
gyration (<S(2)>(z)(1/2)), and intrinsic
viscosity ([eta]) of lentinan and its
fractions in 0.9% NaCl aqueous solution
and dimethyl sulfoxide (Me(2)SO) were
determined by size-exclusion
chromatography combined with multi-angle
laser light scattering (SEC-LLS), LLS, and
viscometry. Analysis of M(w), [eta], and
<S(2)>(z)(1/2) in terms of known theory
for worm-like chains yielded 2240 +/- 100
nm(-1), and 100 +/- 10 nm for molar mass
per unit contour length (M(L)), and
persistence length (q), respectively,
corresponding with theoretical data for
triple-helical chains. The [alpha](D) of
lentinan in water-Me(2)SO mixtures
indicated an order-disorder transition.
The results indicated that lentinan exists
as a triple helix in 0.9% NaCl aqueous
solution and as a single flexible chain in
Me(2)SO. Assays in vivo and in vitro
against the growth of Sarcoma 180 solid
tumor as well as the colorimetric
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) method for lentinan showed
that the triple-helix sample exhibited a
relatively high inhibition ratio.
Interestingly, the triple-helix lentinan
with M(w) of 1.49 x 10(6) exhibited the
highest antitumor activity in vivo, having
an inhibition ratio (xi) of 49.5%, close
to that of 5-fluorouracil (xi = 50.5%),
whereas the bioactivity (xi = 12.3%) of
its single flexible chains almost
disappeared. The triple-helix conformation
plays an important role in enhancing the
antitumor effects of lentinan.
Publication Types:
PMID: 15882854 [PubMed - indexed for
MEDLINE]
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Characterization and immunomodulating
activities of polysaccharide from Lentinus
edodes.
Zheng R,
Jie S,
Hanchuan D,
Moucheng W.
Laboratory of Functional Food and
Nutrition, College of Food Science and
Technology, Huazhong Agricultural
University, Wuhan 430070, PR China.
The polysaccharide L-II was isolated and
purified from the fruiting body of
Lentinus edodes, which consisted of d-glucopyranose
and had the molecular weight of 2.03 x
10(5) Da. We evaluated the effects of the
polysaccharide L-II on the cellular immune
response of Sarcoma 180-bearing mice. Mice
were treated with three doses of the
polysaccharide L-II (1, 5, and 10 mg/kg
body weight) for 10 days. Tumor weight,
relative spleen and thymus weight,
delayed-type hypersensitivity (DTH)
response, phagocytosis of macrophage,
splenocytes proliferation were studied.
Concentration of tumor necrosis
factor-alpha (TNF-alpha), interferon-gamma
(IFN-gamma) and interleukin-2 (IL-2) in
mice serum were measured in control and
polysaccharide groups. At the dose of 1, 5
and 10 mg/kg, a significant increase
(p<0.05) in relative spleen and thymus
weight, DTH, phagocytosis of macrophage
was observed, as well as a significant
decrease in tumor formation. The
concentration of TNF-alpha, IFN-gamma in
serum increased significantly in the
polysaccharide groups compared with the
model control group, but IL-2 not.
Moreover, the polysaccharide L-II could
increase NO production and catalase
activity in macrophages. Results of these
studies demonstrated the antitumor
activity of the polysaccharide L-II on
mice-transplanted sarcoma 180 was mediated
by immunomodulation in inducing T-cells
and macrophage-dependent immune system
responses.
Publication Types:
PMID: 15778117 [PubMed - indexed for
MEDLINE]
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Lentinan from shiitake mushroom (Lentinus
edodes) suppresses expression of
cytochrome P450 1A subfamily in the mouse
liver.
Okamoto T,
Kodoi R,
Nonaka Y,
Fukuda I,
Hashimoto T,
Kanazawa K,
Mizuno M,
Ashida H.
Department of Biofunctional Chemistry,
Faculty of Agriculture, Kobe University,
Rokkodai-cho 1, Nada-ku, Kobe 657-8501,
Japan.
Induction of xenobiotics metabolizing
enzymes is related to the formation and
chemoprevention of cancer. Since
cytochrome P450s (CYPs) including CYP1A
subfamily metabolize certain
pro-carcinogens to their ultimate forms,
down-regulation of CYP1As by food factors
leads to the prevention of cancer.
Mushroom polysaccharides, especially beta-glucans
such as lentinan from Lentinus edodes,
possess the anti-tumor and
immunomodulating activities through the
cytokine production from immunocytes.
Recent our studies have demonstrated that
lentinan suppresses hepatic CYP1As
expression in the both constitutive and
inducible levels through the production of
tumor necrosis factor-alpha and an
increase in the DNA-binding activity of
nuclear factor-kappaB. This paper
discusses on the effective lentinan dosage
and route of administration for
suppression of CYP1As.
PMID: 15630237 [PubMed - indexed for
MEDLINE]
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Lentin, a novel and potent antifungal
protein from shitake mushroom with
inhibitory effects on activity of human
immunodeficiency virus-1 reverse
transcriptase and proliferation of
leukemia cells.
Ngai PH,
Ng TB.
Department of Biochemistry, Faculty of
Medicine, The Chinese University of Hong
Kong, Shatin, New Territories, Hong Kong,
China.
From the fruiting bodies of the edible
mushroom Lentinus edodes, a novel protein
designated lentin with potent antifungal
activity was isolated. Lentin was
unadsorbed on DEAE-cellulose, and adsorbed
on Affi-gel blue gel and Mono S. The
N-terminal sequence of lentin manifested
similarity to endoglucanase. Lentin, which
had a molecular mass of 27.5 kDa,
inhibited mycelial growth in a variety of
fungal species including Physalospora
piricola, Botrytis cinerea and
Mycosphaerella arachidicola. Lentin also
exerted an inhibitory activity on HIV-1
reverse transcriptase and proliferation of
leukemia cells.
Publication Types:
PMID: 14572878 [PubMed - indexed for
MEDLINE]
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Contact dermatitis to Shiitake
mushroom.
Curnow P,
Tam M.
Skin and Cancer Foundation, Melbourne,
Victoria, Australia. paul_mary@myplace.net.au
A 44-year-old woman with occupational
allergic contact dermatitis to Shiitake
mushroom (Lentinus edodes), sawdust and
thiuram. She presented with an 8-month
history of hand and face dermatitis that
developed after working for 2.5 years in a
mushroom farm. Within 3 months of ceasing
work at the farm, her symptoms resolved
completely.
Publication Types:
PMID: 12752194 [PubMed - indexed for
MEDLINE]
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[Immunological study on the antitumor
effects of fungus polysaccharides
compounds]
[Article in Chinese]
Liu C,
Gao P,
Qian J,
Yan W.
Institute of Food Safety Control and
Inspection, Ministry of Health, Beijing
100021, China.
Fungus polysaccharides compounds (FPC) are
the mixture of procyanidins oligomers,
glycyrrhetinicacid and polysaccharides of
hericium erinaceus, lentinus edodes and
poria cocos. The antitumor effects of FPC
and its immunity regulating effects as an
immunostimulant on the mice burdened with
sarcoma 180 (S-180) were studied. FPC
(100, 200 and 400 mg/kg BW) was gavaged to
mice for 31 days. S-180 was transplanted
to these mice on the 21th day. Lentinus
edodes group was gavaged 200 mg/kg BW
saccharine of lentinus edodes. The results
showed that FPC could inhibit the growth
of S-180 effectively. The inhibitory rates
were 37.74%, 44.73% and 48.32%
respectively. The antineoplastic activity
of FPC (200 mg/kg. BW) was more effective
than polysaccharide of lentinus edodes at
the same dose. In S-180 burdened mice, the
percentage of L3T4 and the ratio of
L3T4/Lyt-2, NK activity and the induced
IL-2, IFN-gamma levels were decreased
significantly compared with the normal
control group. As an immunostimulant, FPC
could increase the percentage of L3T4 and
the ratio of L3T4/Lyt-2 in S-180 burdened
mice, but had no significant effects on
the percentage of Lyt-2. Polysaccharide of
lentinus edodes alone could also increase
the immunity competence of mice burdened
with S-180, but was not better than that
of FPC at the same dose. It could be
concluded that the compound of
antineoplastic component could be
synergetic.
Publication Types:
PMID: 12725070 [PubMed - indexed for
MEDLINE]
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Synthesis of beta-(1-->6)-branched
beta-(1-->3) glucohexaose and its
analogues containing an alpha-(1-->3)
linked bond with antitumor activity.
Ning J,
Zhang W,
Yi Y,
Yang G,
Wu Z,
Yi J,
Kong F.
Research Center for Eco-Environmental
Sciences, Chinese Academy of Sciences, PO
Box 2871, Beijing 100085, PR China. fzkong@mail.rcees.ac.cn
A beta-(1-->6)-branched
beta-(1-->3)-glucohexaose, present in many
biologically active polysaccharides from
traditionally herbal medicines such as
Ganoderma lucidum, Schizophyllum commune
and Lentinus edodes, was synthesized as
its lauryl glycoside 32, and its analogues
18, 20 and 33 containing an alpha-(1-->3)
linked bond were synthesized. It is
interesting to find that coupling of a
3,6-branched acylated trisaccharide
trichloroacetimidate donor 9 with
3,6-branched acceptors 13 and 16 with
3'-OH gave the alpha-(1--> 3)-linked
hexasaccharides 17 and 19, respectively,
in spite of the presence of C-2 ester
capable of neighboring group
participation. However, coupling of 9 with
4-methoxyphenyl
4,6-O-benzylidene-beta-D-glucopyranoside
(27) selectively gave beta-(1-->3)-linked
tetrasaccharide 28. Simple chemical
transformation of the tetrasaccharide 28
gave acylated tetrasaccharide
trichloroacetimidate 29. Coupling of 29
with lauryl (1-->6)-linked disaccharide 26
with 3-OH gave beta-(1-->3)-linked
hexasaccharide 30 as the major product.
Bioassay showed that in combination with
the chemotherapeutic agent cyclophospamide
(CPA), the hexaose 18 at a dose of
0.5-1mg/kg substantially increased the
inhibition of S(180) for CPA, but
decreased the toxicity caused by CPA. Some
of these oligosaccharides also inhibited
U(14) noumenal tumor in mice effectively.
Publication Types:
PMID: 12713829 [PubMed - indexed for
MEDLINE]
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Purification and characterization of
acidic proteo-heteroglycan from the
fruiting body of Phellinus linteus (Berk.
& M.A. Curtis) Teng.
Kim GY,
Park HS,
Nam BH,
Lee SJ,
Lee JD.
Department of Microbiology, College of
Natural Sciences, Pusan National
University, Pusan 609-735, South Korea.
Phellinus linteus is a well-known oriental
medicinal fungus that has various
biological activities such as stimulation
of humoral and cell mediated immunity,
anti-mutagenicity activity, and
anti-cancer activity. The process of
isolating and purifying a water-soluble
glycan from P. linteus was achieved by hot
water extraction, filtration, solvent
precipitation, dialysis, and
freeze-drying. Acidic fractions of the
polysaccharide were separated from crude
polysaccharides by DEAE-cellulose anion
exchange chromatography at 0.4 M NaCl. The
molecular weight of the
proteo-heteroglycan after Sepharose CL-4B
gel filtration chromatography was about
150,000. The acidic proteo-heteroglycan
consisted of 72.2% polysaccharide and
22.3% protein. The sugar of the
proteo-heteroglycan was composed of
mannose, galactose, glucose, arabinose,
and xylose. The amino acid pattern showed
that the fractions contained large amounts
of aspartic acid, glutamic acid, alanine,
glycine, and serine. The fractions for
both alpha-glycan at 860 cm(-1) and beta-glycan
at 910 cm(-1) had the characteristics of
IR spectrum absorption as compared to
those for beta-glucan derived from
Lentinus edodes. A 13C and 1H NMR
spectroscopy showed that the acidic
proteo-heteroglycan was a noble
biomolecule mixed both alpha- and
beta-linkages, and a (1,6) branched type
(1,3) glycan.
Publication Types:
PMID: 12676504 [PubMed - indexed for
MEDLINE]
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Inhibition of human colon carcinoma
development by lentinan from shiitake
mushrooms (Lentinus edodes).
Ng ML,
Yap AT.
Department of Microbiology, National
University of Singapore, Singapore.
micngml@nus.edu.sg
OBJECTIVES: Lentinan was extracted from
shiitake mushrooms (Lentinus edodes) via a
new cost-effective procedure that resulted
in high purity (88%) and yield. Unlike
previous reports whereby the lentinan was
given parenterally, in this study the
emphasis was on the oral administration of
lentinan. The goal is to document whether
the efficacy of the antitumor property is
still expressed through this route of
administration. DESIGN: Initial study on
the action of lentinan was conducted using
murine lymphoma (K36) cells in a AKR mouse
model. Further investigation on the
effectiveness of the extracted lentinan
was then performed using human
colon-carcinoma cell lines in mice. Six
established human colon-carcinoma cell
lines segregated into three groups of
different degrees of differentiation were
used in this study. One group was not fed
(control) and the second group was prefed
with lentinan for 7 days prior to
inoculations with the cancer cells. The
size of the tumors that developed was
rated after 1 month. RESULTS: Significant
regression in tumor formation was observed
in prefed mice compared to control (unfed)
mice when K36 or human colon-carcinoma
cells were used. Significant reductions in
the size of the tumors were observed in
mice prefed with lentinan. Follow-up
investigation proceeded with the use of
nude mice (athymic). Lymphocytes extracted
from AKR mice prefed with lentinan for 7
days were inoculated into the nude mice.
This was then followed by inoculation of
the human colon-carcinoma cell lines into
these mice. Much smaller tumors were
formed in nude mice inoculated with
lymphocytes, in contrast to the larger
tumor formed in nude mice without
lymphocytes inoculation. CONCLUSION: This
study showed that the antitumor property
of lentinan was maintained with oral
administration. In addition, "primed"
lymphocytes, when given passively to
immunodeficient mice, were able to retard
the development of tumors in these mice.
Publication Types:
PMID: 12470439 [PubMed - indexed for
MEDLINE]
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Effects of a mushroom mycelium extract
on the treatment of prostate cancer.
deVere White RW,
Hackman RM,
Soares SE,
Beckett LA,
Sun B.
Department of Urology, University of
California, Davis, School of Medicine,
Sacramento, California 95817, USA.
OBJECTIVES: To determine whether
supplemental amounts of a
polysaccharide/oligosaccharide complex
obtained from a shiitake mushroom extract
(SME) would lower the prostate-specific
antigen (PSA) level in patients with
prostate cancer. METHODS: A total of 62
men (mean age 73.2 years, range 53.6 to
85.5) with histologically proven prostate
cancer who had two consecutive elevated
PSA readings were accrued to the study
during a 3-month period. This was an
open-label study in which the patients
received oral administration of capsules
containing SME given three times daily for
6 months. The endpoint for the trial was
the lowering of the PSA levels. RESULTS:
Of the 62 men enrolled in the study, 61
were assessable. At 4 months, 1 patient
withdrew because of unrelated surgery and
7 withdrew because of disease progression;
none had responded with a decrease of
greater than 50% in the PSA level. By 6
months, a total of 23 patients had
progression and none had responded.
Thirty-eight patients had stable PSA
levels after 6 months. Although not the
primary endpoint of the study, in other
studies these patients could have been
included as responders. When the patients'
rates of PSA rise before study entry were
analyzed, 4 (7%) had stabilized disease
while taking SME. Thus, the final results
for our study patients were 0 with a
complete response, 0 with a partial
response, 4 (7%) with stable disease, and
23 of 61 with progression while taking SME.
CONCLUSIONS: SME alone is ineffective in
the treatment of clinical prostate cancer.
Publication Types:
PMID: 12385925 [PubMed - indexed for
MEDLINE]
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Chronic hypersensitivity pneumonitis
induced by Shiitake mushroom spores
associated with lung cancer.
Suzuki K,
Tanaka H,
Sugawara H,
Saito Y,
Koba H,
Tsunematsu K,
Abe S.
Third Department of Internal Medicine,
Sapporo Medical University School of
Medicine.
A 61-year-old man was admitted to our
hospital with a 6-month history of
productive cough. He, along with his wife,
had been involved with Shiitake mushroom
cultures for a period of 12 years. On
admission, chest radiography showed
bilateral fine-nodular shadow and CT scans
showed reticulonodular opacities and a
ground-glass appearance predominantly in
the subpleural area in both lungs, and a
mass in the left S6. Resected pathological
specimens obtained by left lower lobectomy
revealed lung adenosquamous carcinoma
(stage IB), interstitial changes
accompanied with lymphocyte proliferation
and fibrosis, and granuloma with giant
cells. Serum precipitins for Shiitake
mushroom antigens were positive. The
productive cough improved after the
hospital admission and occurred again when
he returned to work with the Shiitake
mushroom production. Therefore, chronic
hypersensitivity pneumonitis (HP) caused
by Shiitake mushroom spores was diagnosed.
Moreover, his wife was found to have HP
caused by mushrooms at this time. There
are only two previous reports of chronic
HP caused by Shiitake mushroom in Japan,
and this is the first case of chronic HP
associated with lung cancer.
Publication Types:
PMID: 11757770 [PubMed - indexed for
MEDLINE]
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-
[Intratumoral administration of
biological preparations--recommendation
for integrative medicine]
[Article in Japanese]
Ebina T.
Division of Immunology, Research
Institute, Miyagi Cancer Center.
The antitumor effect of biological
preparations was examined in a double
grafted tumor system. PSK is a hot water
extract of cultured mycelia from Coliolus
versicolor. Its protein content is about
38% and the main glycoside portion of PSK
is beta-D-glucan. Lentinan is purified
from fruit bodies of Lentinus edodes and
is a beta-1, 3-glucan. Cepharanthin is an
extract from the root of Stephania
cepharantha HAYATA, consisting of 4 kinds
of biscoclaurine alkaloids. TAHEEBO tea is
a hot water extract of Tabebuia
avellanedae, the active ingredient of
which is naphthoquinones. If protein-bound
polysaccharides were to be used in Western
medicine, these polysaccharides would be
purified, but purified beta-glucan loses
its beneficial effects. Similarly, when
raw Cepharanthin is purified to isolate
its active ingredient (an alkaloid
cepharanthine), its anti-tumor effect is
weakened. Clear IAP induction was observed
in serum of mice treated with extracts of
Coliolus versicolor and Stephania
cepharantha. However, IAP induction was
not observed in the serum of mice treated
with purified beta-glucan or purified
alkaloid. This suggests that macrophages
may recognize extracts but not purified
substances. In Western medicine, purified
substances with known chemical structures
are recognized as drugs, but overdoses of
these drugs are toxic to the body, thus
adverse reactions are always an issue. In
Chinese medicine, mixtures containing
several crude drugs are recognized as
drugs, whose active ingredients are not
identified. In integrative medicine, drugs
are extracts that contain active
ingredients with known structures and
functions. We propose a Japanese version
of integrative medicine which is neither
Western nor Chinese.
Publication Types:
PMID: 11707968 [PubMed - indexed for
MEDLINE]
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-
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.
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.
Publication Types:
PMID: 10702635 [PubMed - indexed for
MEDLINE]
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