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The scientific information in this journal is educational and is not to be used as a substitute for a doctor's care or for proven therapy.
PROVIDING SCIENTIFIC INFORMATION RELATED TO NUTRITIONAL SACCHARIDES AND OTHER DIETARY INGREDIENTS.
APRIL 1, 2000 VOL 1, NO 14

EXTERNAL EDITORIAL BOARD MANNATECH INCORPORATED

INTERNAL EDITORIAL BOARD
Tom Gardiner, PhD Doris Lefkowitz, PhD Stephen Boyd, PhD, MD
Global Health Safety Environment and Associate Clinical Professor of Microbiology Kathryn Dykman, MD
Regulatory Affairs Coordinator University of South Florida John Hall, DDS
Shell Chemical Company (Retired) College of Medicine Bill McAnalley, PhD
Houston, Texas Tampa, Florida H. Reginald McDaniel, MD
Bob Ward, PED
James C. Garriott, PhD, D-ABFT Stanley S. Lefkowitz, PhD
Professor (Clinical Adjunct Faculty) Professor of Microbiology and Immunology TECHNICAL STAFF
Kia Gary, RN
University of Texas Health Science Center Texas Tech School of Medicine
Eric Moore, DChem
Consulting Toxicologist Lubbock, Texas
Jane Ramberg, MS
San Antonio, Texas
Robert K. Murray, MD, PhD GRAPHIC ARTIST
Alice Johnson-Zeiger, PhD Professor (Emeritus), Biochemistry Bruce Peschel
Professor of Biochemistry (Retired) University of Toronto
University of Texas Health Center Toronto, Ontario, Canada EDITOR IN CHIEF
Tyler, Texas Eileen Vennum, RAC

Glyconutritionals: Implications for Cancer

Stanley Lefkowitz, PhD

One of the most feared words in the English language is
cancer. This word, and its implications, can cause a state of
anxiety, anguish, and depression. Virtually all of us, if we
live long enough, will have to deal with it either directly, or
indirectly through one of our loved ones. In our lifetime,
one out of every two men and one out of every three
women will develop some form of cancer. In the United
States today there are an estimated 1.2 million new cases of
cancer this year compared to an estimated 10 million cases
of cancer worldwide. More than 560,000 lives were lost to
cancer last year, making it the second leading cause of death
in the United States.1
Many approaches have been tried and many billions of
dollars have been spent to treat various cancers with vary-
ing degrees of success. One approach which has not had
wide-spread acceptance to date, but has become quite
intriguing, is the dietary use of certain carbohydrate-con-
taining plant materials or glyconutrients to either prevent
or treat certain cancers. There are literally hundreds of
reports in the literature describing beneficial effects of sug-
ars/carbohydrates in various animal models; however, not
all of the reports are concerning animals. A recent and quite
interesting presentation at a major national meeting calls
for the use of nutritional and dietary supplements in con-
junction with standard cancer therapy to improve both
prognosis and quality of life.2
It is known that certain foods, including many vegetables
and fruits, may offer some positive effects in the fight
against cancer. There are numerous references which under-
score the importance of a diet obtained primarily from plant
sources as a major step in preventing cancer, or at least ben-
efiting cancer patients3-7 The isolation of the specific chemi-
cal/s involved in protection against cancer has proven diffi-
cult. Nevertheless, certain phytochemicals have demon-
strated some efficacy, using either animal tumor models or
human retrospective studies. A number of these chemicals
function primarily as antioxidants. Among the most well
known antioxidants are the following: vitamin A and its
analogs, C and E, as well as other substances which have no
known nutritional value. Other studies have focused on
high-fiber diets and their ability to reduce cancers, includ-
ing those of the colon and breast.8,9 Studies demonstrating
anticancer potential are difficult to perform and require a
major time investment; however, prevention is far more
efficient as well as economical when compared to treat-
ment.
The role of carbohydrates, including simple sugars, has
only recently come under study. Glycoproteins are proteins
which have carbohydrates as part of their structure. Many of
the tissue and blood group antigens have carbohydrate
groups. Many of these carbohydrates have been found to
change during cancer.10,11 Understanding the functional sig-
nificance of these changes is not possible with existing
knowledge; however, awareness of these changes may be

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useful for both diagnosis and immunotherapy. Many of
these changes relate to adhesion properties, or the ability of
cancer cells to stick to other cells, as well as to metastasis of
cancer cells. 12 These glycoproteins may also relate to the
ability of the tumor to avoid immune responses of the host.
Altered glycoproteins have been found in intestinal cancer,
pancreatic cancers, hepatomas, and ovarian, prostate and
lung cancers, etc. 10,11
A number of reports are coming out in the literature
describing the isolation and identification of both polysac-
charides and glycoproteins from plant and other sources
which have anti-tumor properties. A number of anti-tumor
compounds have been isolated from fungi and other
sources. 13-16 Studies in our own laboratory have demonstrat-
ed that proteins which have mannose sugars on their sur-
face can activate the macrophage, 17-19
one of the most impor-
tant cells involved in fighting cancer. Binding of mannose
to their cell surfaces not only activates macrophages, but
also induces these cells to secrete substances which stimu-
late other cells of the immune system. For example,
macrophages will secrete interferons which will activate
natural killer cells, another white blood cell involved in
elimination of cancer cells. Recognition of the importance
of mannose in the regulation of the immune system has
been reported by others. 20
A wealth of literature, including numerous experiments
and treatments, describes significant efficacy of these sub-
stances under specific conditions. An interesting report
describes exceptional results using high dose glucose inject-
ed intraperitoneally (IP) for the treatment of stage III ovari-
an cancer in women. 21 Acemannan is a long chain of man-
nan polymers with random o-acetyl groups. A number of
reports in the literature have described the immunomodu-
latory properties of injectable acemannan and its efficacy
for the treatment of certain tumors including Norman sar-
coma in mice 22 and canine and feline fibrosarcomas. 23
A gly-
conutritional mixture injected into mice with Norman sar-
coma cells resulted in over 50% survivors as compared to
untreated mice with no survivors. 24
A highly branched poly-
saccharide known as arabinogalactan, which is composed of
a galactose backbone with side chains of galactose and ara-
binose, has also been demonstrated as an immune stimu-
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GlycoScience Vol. 1, No. 14
lant, which can block experimental liver metastasis when
injected IP. 25,26 Other sugars have also been utilized for can-
cer with considerable success including intravenous infu-
sion of fucose for the treatment of a transplantable breast
cancer in rats. 27-29 The addition of certain individual sugars
including D-mannose, D-ribose, and D-glucosamine into
the drinking water or administered intraperitoneally to mice
carrying Ehrlich ascites tumor cells enhanced their sur-
vival. 30 Addition of inulin and oligofructose to rodent diets
reduced incidence of several tumors. 31,32
Intravenous infu-
sion of D-glucosamine inhibited the growth of a trans-
plantable carcinoma in rats. 33
In vitro studies showed that
the addition of fucose, mannose, glucose, or galactose
inhibited the growth of malignant cells in a dose-dependent
manner with fucose and mannose as the most effective. 34
The above represents just a sample of the literature
describing "anti-cancer’ effects of glyconutrients. There are
literally hundreds of reports supporting this concept. Today
the "prevention" of cancer with proper nutrition is widely
accepted. We believe, in time, the efficacy of these materials
in the fight against cancer will be firmly established, and
that alternative choices for treatment will be included in the
armamentarium for the treatment of cancer.
Finally, our understanding of oncogenes and tumor sup-
pressor genes, as well as many of the factors which cause
35
mutations of those genes, does not preclude acceptance of
nutrition as a major factor in cancer development.
Molecular events, immune responses to tumor initiation,
and metastasis are still potentially under the influence of
our diet. Further research will undoubtedly shed additional
light on this important issue.
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Acta Anatomica 1998;161:36-79.
11. Hakomori S. Cancer-associated glycosphingolipid antigens: their structure, organization, and function.
Acta Anatomica 1998;161:79-90.
12. Kaltner H, Stierstorfer B. Animal lectins as cell adhesion molecules. Acta Anat.(Basel) 1998;161:162-179.
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Proc Soc Exp Biol Med 1999;221:281-293.
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perspective. Crit Rev Immunol 1999;;%19:65-96.
15. Ng TB. A review of research on the protein-bound polysaccharide (polysaccharopeptide, PSP) from the mushroom
Coriolus versicolor (Basidiomycetes: Polyporaceae). Gen.Pharmacol 1998;30:1-4.
16. Yamazaki M. Antitumor and antimicrobial glycoproteins from sea hares. Comp Biochem Physiol C. 1993;105:141-146.
17. Mone J, Lefkowitz SS. Induction of interferon synthesis and cytotoxicity by murine peritoneal macrophages exposed
to glycoprotein ligands. Acta Virol 1992;36:383-391.
18. Stuart RW, Lefkowitz DL, Lincoln JA, Howard K, Gelderman MP, Lefkowitz SS. Upregulation of phagocytosis and
candidicidal activity of macrophages exposed to the immunostimulant acemannan.
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19. Lefkowitz DL, Lincoln JA, Lefkowitz SS, Bollen A, Moguilevsky N. Enhancement of macrophage-mediated bactericidal
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20. Tizard IR, Carpenter RH, McAnalley BH, Kemp MC. The biological activities of mannans and related complex
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Invasion Metastasis 1991;11:348-355.
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