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Marked Inhibition of Tumor Growth, MMP
Secretion and Invasion by a Nutrient Mixture on Head and Neck Squamous Carcinoma Cell
Line FaDu: In Vitro and In Vivo Studies
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, Oncology, 1260 Memorex Drive, Santa Clara, CA 95050
Presented at:18th EORTC-NCI-AACR Symposium on Molecular
Targets and Cancer Therapeutics, November 7-10, 2006, Prague, Czechoslovakia
Published in: The European Journal of Cancer 2006,
vol 4(12), abstract #520.
Abstract
Background:
Head and neck squamous cell carcinomas (HNSCC), the sixth most common malignancies in
the United States, are known for their aggressive growth and propensity to invade and
metastasize. We investigated the effect of a novel nutrient mixture (NM) containing ascorbic
acid, lysine, proline, and green tea extract on human HNSCC cell line FaDu in vitro, evaluating
viability, MMP secretion, invasion and morphology. In vivo studies were carried out in
athymic nude mice bearing HNSCC FaDu xenografts.
Methods:
After one week of isolation, 5-6 weeks old athymic male nude mice were inoculated with
3x106 FADU cells 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 on FaDu cells, measuring cell proliferation by
MTT assay, invasion through Matrigel, morphology by H&E staining, and secretion of
MMPs by gelatinase zymography. Cells were also treated with PMA for MMP-9 induction.
Results:
NM strongly inhibited the growth of tumors by 50%. In vitro, NM exhibited
dose response toxicity with maximum toxicity of 50% over the control at
1000 mg/ml. Zymography showed only a faint band representing MMP-2 and
PMA-induced MMP-9. NM inhibited secretion of both MMP-2 and MMP-9 in a
dose dependent fashion, with virtual total inhibition at 1000 mg/ml.
Invasion through Matrigel was inhibited at 50, 100 and 500 mg/ml by 75%,
85% and 100% respectively. H&E staining did not indicate changes up to
100 µg/ml.
Conclusion:
In conclusion, NM has a great potential for therapeutic use in the
treatment of HNSCC by suppressing tumor growth and significantly
inhibiting MMP secretion and invasion of HNSCC cells in vitro.
Comment:
Head and neck squamous cell carcinomas (HNSCC), the sixth most common malignancies
in the United States, are known for their aggressive growth and propensity to invade
and metastasize. We investigated the effect of a novel nutrient mixture (NM) containing
ascorbic acid, lysine, proline, and green tea extract, shown to have potent antitumor
effects on many cancer cell lines, on the growth of human HNSCC xenografts in athymic
nude mice, as well as investigating this cell line in vitro, evaluating viability,
MMP secretion, invasion and morphology. NM inhibited the growth of tumors by 50% and
exhibited dose-response toxicity to cells in vitro, with 50% toxicity at 1000 µg/ml.
In addition, NM inhibited the invasive parameters of MMP secretion and Matrigel invasion
by cells in a dose-dependent manner with total block of MMPs at 1000 µg/ml and invasion
at 500 µg/ml. These results are significant as they suggest that NM, a relatively
safe therapeutic agent, has great potential in treatment of HNSCC in suppressing tumor
growth and metastasis. |
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