New kind of chemotherapy kills cancer cells

ironjustice@aol.com · medicine forum Guru Joined: 28 Apr 2005 Posts: 1522

http://www.ceps.unh.edu/news/releases03/planalpprint.htm

UNH Awarded Patent for Cancer Treatment

New kind of chemotherapy kills cancer cells

DURHAM, N.H. --DURHAM, N.H. - The University of New Hampshire (UNH)
has been granted a U.S. patent for a new way to kill cancer cells.

Roy Planalp, associate professor of chemistry in the UNH College of
Engineering and Physical Sciences, invented the novel chemotherapy in
collaboration with researchers at the National Institutes of Health
(NIH) and Wake Forest University Health Sciences in Winston-Salem,
N.C., which share the patent with UNH.

"This invention is exciting because it has significant potential for
cancer therapy," said Robert Dalton, director of the UNH Office of
Intellectual Property Management. "It also has potential for other
therapeutic areas as well."

Planalp and his collaborators, funded by a grant from NIH's National
Cancer Institute, found that they could kill cancer cells by starving
them of the essential nutrient iron. The treatment employs molecules
called chelators (KEE-late-ors), which bind tightly with metal. The
chelators that best bind iron are in the tachpyr family of substances
and are shaped like an open, six-fingered claw. They suck iron in and
then snap closed, like a spring-loaded trap.

"Iron is like money. It's an essential nutrient that's not always
bioavailable, so cells store iron and release it as needed,"
explained Planalp. "What the chelators do is come in and rob the iron
bank just as the cell is making a withdrawal, so the cell makes another
withdrawal, and if there are more chelators, that gets robbed too. This
continues until the bank is empty and the cell can't function
anymore."

Encased by the chelator, the iron is no longer available to perform its
role in vital jobs like transporting oxygen, and the cancer cell dies.
The chelator, still holding tightly to the iron, is quickly removed
from the blood by the liver and expelled from the body. Side effects
are expected to be negligible as iron chelators are already used to
treat people with too much iron in their blood.

Planalp stumbled on the cancer-fighting potential of chelators while
experimenting with using them as diagnostic agents. While testing a
chelator bound to gallium, a metal that shows up well in CAT scans, he
found it discarded the gallium in favor of the iron needed by cells,
causing them to die. "We didn't expect this," said Planalp, "so
we decided to pursue it."

Animal testing at the NIH showed that iron chelators are effective at
killing several kinds of cancer cells and they are quickly removed by
the liver - too quickly, in fact. Planalp and his collaborators are
currently investigating ways to either keep iron chelators in the body
longer or speed them up so they can finish the job before they are
removed.

Chelators tailored to bind to toxic metals, such as mercury, chromium
or lead, may have other therapeutic applications. "It's all about
selectivity," said Planalp. "There's a whole set of challenges
out there for detoxification."

Awarded in July, the patent is now being marketed by Wake Forest to
companies which can turn the idea into a marketable product. Like
existing chemotherapy drugs, iron chelators will most likely be used in
a chemical "cocktail" containing other chemotherapy agents.

CAPTION

Spring-loaded trap: A drawing depticts a tachpyr molecule in its open
position, before it has bound with a metal, and in its closed position,
after it has sucked in the metal and trapped it.

###

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ironjustice@aol.com · medicine forum Guru Joined: 28 Apr 2005 Posts: 1522

ironjustice@aol.com wrote:

<<snip>>
mineral binding ability
<<snip>>

MEDICAL ABSTRACTS

* Antioxidant functions of phytic acid.
* Dietary suppression of colonic cancer. Fiber or phytate?
* Phytic acid in health and disease.
* Phytic acid and minerals: effect on early markers of risk for
mammary and colon carcinogenesis.

PUBLISHED ARTICLES

* Natural Sugar-Phosphate Compound Shows Promise as Cancer
Treatment
* The Cancer Stopper
_________________________________________________________________

MEDICAL ABSTRACTS

Antioxidant functions of phytic acid.
Graf E, Eaton JW
Pillsbury Company, Technology Center, Minneapolis, MN 55414.
Free Radic Biol Med 1990;8(1):61-9

Phytic acid is a natural plant antioxidant constituting 1-5% of most
cereals, nuts, legumes, oil seeds, pollen and spores. By virtue of
forming a unique iron chelate it suppresses iron-catalyzed oxidative
reactions and may serve a potent antioxidant function in the
preservation of seeds. By the same mechanism dietary phytic acid may
lower the incidence of colonic cancer and protect against other
inflammatory bowel diseases. Its addition to foods inhibits lipid
peroxidation and concomitant oxidative spoilage, such as
discoloration, putrefaction, and syneresis. A multitude of other
industrial applications are based on the antioxidant function of
phytic acid.
_________________________________________________________________

Dietary suppression of colonic cancer. Fiber or phytate?
Graf E, Eaton JW
Cancer 1985 Aug 15;56(4):717-8

The incidence of colonic cancer differs widely between various human
populations. It has been suggested that dietary fiber content is of
utmost importance and is inversely related to the occurrence of
colonic cancer. However, high-fiber diets are not always correlated
with low frequency of colonic cancer, suggesting the involvement of
additional dietary constituents. Inositol hexaphosphate (phytic
acid)
is an abundant plant seed component present in many, but not all,
fiber-rich diets. The authors have found that phytic acid is a
potent
inhibitor of iron-mediated generation of the hazardous oxidant,
hydroxyl radical. Herein, the authors propose that inhibition of
intracolonic hydroxyl radical generation, via the chelation of
reactive iron by phytic acid, may help explain the suppression of
colonic carcinogenesis and other inflammatory bowel diseases by
diets
rich in phytic acid.
_________________________________________________________________

Phytic acid in health and disease.
Zhou JR, Erdman JW Jr.
Division of Nutritional Sciences, University of Illinois, Urbana
61801, USA.
Crit Rev Food Sci Nutr 1995 Nov;35(6):495-508

Phytic acid (PA), a major phosphorus storage compound of most seeds
and cereal grains, contributes about 1 to 7% of their dry weight. It
may account for more than 70% of the total kernel phosphorus. PA has
the strong ability to chelate multivalent metal ions, especially
zinc,
calcium, and iron. The binding can result in very insoluble salts
that
are poorly absorbed from the gastrointestinal tract, which results
in
poor bioavailability (BV) of minerals. Alternatively, the ability of
PA to chelate minerals has been reported to have some protective
effects, such as decreasing iron-mediated colon cancer risk and
lowering serum cholesterol and triglycerides in experimental
animals.
Data from human studies are still lacking. PA is also considered to
be
a natural antioxidant and is suggested to have potential functions
of
reducing lipid peroxidation and as a preservative in foods. Finally,
certain inositol phosphates, which may be derived from PA, have been
noted to have a function in second messenger transduction systems.
The
potential nutritional significance of PA is discussed in this
review.
_________________________________________________________________

Phytic acid and minerals: effect on early markers of risk for
mammary
and colon carcinogenesis.
Thompson LU, Zhang L
Department of Nutritional Sciences, Faculty of Medicine, University
of
Toronto, Ontario, Canada.
Carcinogenesis 1991 Nov;12(11):2041-5

This study determined the effect of inositol hexaphosphate or phytic
acid (PA; 1.2%), Ca (1.5%) and Fe (535 p.p.m.) alone, and PA in
combination with Ca or Fe in a high-fat diet (25%) on the labeling
(LI) and mitotic (MI) cell proliferation indices, nuclear aberration
(NA) and intraductal proliferation (IDP) in the mammary gland, as
well
as the LI in colonic epithelial cells. Diet supplementation with PA
alone caused reductions (P less than 0.05) in the colon LI by 18%,
and
in the LI and NA in the total mammary gland structures of mice by 29
and 30% respectively. Supplementation with Fe or particularly Ca
caused increases in the colon LI and in the mammary LI, MI, NA and
IDP
but these were reduced by 25-53% (P less than 0.05) in the presence
of
PA. These results support the hypothesis that PA may reduce the risk
for both colon and mammary cancer and its effect is related to its
mineral binding ability. Furthermore, significant relationships (P
less than 0.01) were observed between the LI and MI or NA in the
total
structures of the mammary gland. The number of IDPs also related (P
less than 0.05) to LI or NA in the terminal end bud structure of the
mammary gland, suggesting that highly proliferating mammary cells,
particularly in the terminal end bud structure, are of greater risk
for nuclear damage and development to IDP. A significant
relationship
(P less than 0.01) was observed between the cell proliferation in
the
mammary gland and that in the colon, indicating that both tissues
can
be influenced similarly by dietary constituents.
_________________________________________________________________

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