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Inhibition
of Hemangioendothelioma In Vivo and Invasion and
Growth In Vitro by a Unique Nutrient Mixture
M.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
Dr. Rath Research Institute, Oncology Division, Santa Clara, CA
95050
Presented at: 47th Annual Meeting of the American
College of Nutrition, October 5-8, 2006, Reno, NV
Published in: Journal of the American College
of Nutrition vol 25(5), October 2006, abstract #23
Abstract
Introduction:
Hemangiomas, the most frequent vascular tumors in Caucasian infants,
occur in approximately 1% of normal newborns, but the incidence
increases to 20% in premature infants weighing less than 1000
gm. These lesions are characterized by rapid proliferation of
capillaries during the first year of life, followed by a slowed
growth and regression of the tumor over the next 5-6 years, with
complete regression of the lesion by the age of 6-12 years. Approximately
5% of hemangiomas cause serious tissue damage, while 1-2% are
life threatening. However, the pathogenesis of these tumors is
still largely unknown and the current therapy, such as systemic
corticosteroid, vincristine, and interferon-alpha, is toxic and
remains unsatisfactory. A nutrient mixture (NM) containing lysine,
proline, ascorbic acid and green tea extract has shown significant
anti-angiogenic and anti-tumor effect against a number of cancer
cell lines.
Objective:
Using a mouse hemangioendothelioma model, we investigated the
efficacy of NM. We also tested the effect of NM in vitro,
evaluating viability, MMP secretion, invasion and morphology.
Methods:
Athymic nude mice, 5-6 weeks old, were inoculated with 3x106 EOMA
cells (ATCC) subcutaneously and randomly divided into two groups;
group A was fed a regular diet and group B a regular diet supplemented
with 0.5% NM. Four weeks later, the mice were sacrificed and their
tumors were excised, weighed and processed for histology. We also
tested the effect of NM in vitro, measuring cell proliferation
by MTT assay, invasion through Matrigel, morphology by H&E
staining, and secretion of MMPs by gelatinase zymography at 0,
10, 50, 100, 500 and 1000 µg/ml concentration, in triplicate
at each dose.
Results:
NM inhibited the growth of tumors by 50%. In vitro, NM
exhibited dose response toxicity with 10%, 30% and 55% at 10,
100 and 1000 µg/ml. Invasion through Matrigel was inhibited
at 10, 50, 100 and 500 µg/ml by 20%, 25%, 30% and 100% respectively.
H&E did not indicate any changes even at highest concentration.
Interestingly EOMA cell did not demonstrate any MMP activity by
zymography.
Conclusions:
These results suggest that NM may have therapeutic potential in
treating infantile hemangioendotheliomas and, perhaps, other cutaneous
vascular tumors.
Comment:
Current treatment for infantile hemangioendothelioma includes
toxic agents such as systemic corticosteroids, vincristine,
and interferon-alpha. We investigated the effect of a unique
non-toxic micronutrient mixture (NM) containing lysine, proline,
ascorbic acid and green tea extract, which has shown significant
anti-angiogenic and anti-tumor effect against a number of
cancer cell lines, on nude mice injected subcutaneously with
EOMA cells. In addition, we tested NM in vitro on EOMA cells
evaluating its effect on cell proliferation, invasion, and
cell morphology. NM inhibited the growth of tumors by 50%
and exhibited dose response toxicity and inhibition of EOMA
Matrigel invasion. EOMA cell morphology was not affected even
at highest concentration tested. These results are significant
as they indicate NM is a potential non-toxic alternative agent
for treatment of infantile hemangioendothelioma. |
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