| Inhibition
of 7,12-Dimethylbenzanthracene-Induced Skin Tumor by a Nutrient
Mixture
M.W. Roomi, N.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
Dr. Rath Research Institute, Oncology Division,
1260 Memorex Drive, Santa Clara, CA
Presented at: 98th Annual Meeting of the AACR,
Los Angeles, CA, April 14-18, 2007
Published in: Proceedings of the 98th Annual
Meeting of the AACR,
Abstract #2634, p 231
Abstract
Introduction:
Skin cancer, the most common of all human cancers, accounts for
half of all cancers diagnosed. The annual incidence of all forms
of skin cancer is increasing each year, and is a growing public
concern. It has been estimated that nearly half of the Americans
who live to the age of 65 will develop skin cancer. We have developed
strategies to inhibit cancer development and its spread using
naturally occurring nutrients such as lysine, proline, ascorbic
acid and green tea extract (NM). Such a unique formulation was
shown to exhibit synergistic anticancer activity in vivo and in
vitro in a number of cancer cell lines including human and murine
melanoma cells lines, inhibiting cancer cell growth, MMP secretion,
invasion, metastasis, and angiogenesis. The present study examines
the in vivo effect of NM on the development of skin cancer induced
by 7,12-dimethylbezanthracene (DMBA) in female SENCAR mice by
a complete carcinogenesis protocol.
Methods:
The dorsal area of 55 female SENCAR mice was carefully shaved
with an electric clipper to avoid cuts and bruises. The mice were
then divided into groups: 1-4. After two days the mice in the
groups 1 (n=10), 3 (n=20) and 4 (n=20) were treated topically
with 100 nM DMBA in 0.2ml of acetone twice a week for four weeks.
Group 1 mice were fed the regular diet. Group 2 (n=5) mice received
only acetone 0.2 ml twice for four weeks and fed a regular diet.
Group 3 mice were further divided into two sub groups; 3A and
3B. Group 3A (n=10) mice were fed a regular diet containing 0.5%
NM from the day of DMBA treatment and group 3B (n=10) mice were
fed the regular diet and received NM (75 mg in 0.4 ml of 1:1 acetone/water)
topically to the shaved area 15 minutes before DMBA application
twice a week for 4 weeks. Group 4 mice were fed a regular diet
containing 0.5% NM for two weeks prior to the application of DMBA.
At this time, the mice were further divided into two groups. Group
4A (n=10) was fed the 0.5% NM diet as in 3A and 4B (n=10) the
regular diet as described for 3B. Body weight and diet consumption
of the mice were monitored and the skin tumors (papillomas) were
counted and recorded. Ten weeks thereafter the mice were euthanized,
skinned, and tumors were processed for histology.
Results:
NM inhibited DMBA induced skin tumor incidence and multiplicity
by 59%, 62%, 69%, 86% in groups 3A, 3B, 4A, 4B respectively.
Conclusion:
These results suggest that NM has strong potential as a useful
therapeutic regimen for skin cancer by significantly inhibiting
the number of papillomas and the incidence and tumor multiplicity
of DMBA induced skin tumors.
Comment:
The annual incidence of skin cancer, the most common of all
human cancers, is increasing each year. Nearly half of Americans
who live to the age of 65 will develop skin cancer. We examined
the effect of a unique nutrient mixture (NM) that contains
lysine, proline, ascorbic acid and green tea extract on the
development of skin cancer induced by topical application
of 7,12-dimethylbezanthracene (DMBA) in female SENCAR mice.
Groups of mice were treated with NM by diet and or topically
or with saline. NM significantly inhibited DMBA-induced skin
tumors. Topical NM treatment prior to DMBA application was
the most effective treatment (reducing the incidence of skin
tumors by 86%), followed by 2-week pretreatment with a diet
enriched with NM (69% reduction in tumors) and treatment with
dietary NM during the study (59% reduction in tumors). These
results are significant as they indicate that NM has strong
potential as a therapeutic regimen for prevention and treatment
of skin cancer. |
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