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Anti-Tumor Effect
of Nutrient Synergy: A Novel MMP Inhibitor in Pancreatic Cancer
Cell Line MIA PaCa-2 (2003) Roomi MW, Ivanov
V, Niedzwiecki A, Rath M.
Presented at: AACR-NCI-EORTC International
Conference on Molecular Targets and Cancer
Boston, MA, November 17-21, 2003
Abstract
Introduction:
Matrix metalloproteinases (MMPs) have received much attention
in recent years for their role in various malignancies, and have
been implicated in tumor invasion, metastasis and angiogenesis.
We have recently shown in vitro that Nutrient Synergy (NS), a
novel formulation consisting of lysine, proline, arginine, ascorbic
acid, and EGCG, inhibits MMP expression in cells, invasion, and
metastasis in a number of cancers, including breast, prostate,
colon, and melanoma. NS also suppressed the growth of these tumors,
without any adverse effects, in nude mice. In the current study,
we investigated the effect of NS in pancreatic cancer. Cancer
of pancreas continues to be a major unsolved health problem, causing
approximately 28,000 deaths in US and 50,000 deaths in Europe
each year. Pancreatic cancer is the fourth leading cause of cancer-related
deaths in both men and women.
Objective:
We investigated the effect of NS on pancreatic cancer cell line
MIA PaCa-2 for viability, MMP expression, invasion, and morphology.
Methods:
Viability or cytotoxicity was evaluated based on cell proliferation
by MTT assay and MMP expression in condition media by gelatinase
zymography. Invasion through Matgrigel was assayed and morphology
was observed by Hematoxylin and Eosin staining.
Results:
- NS was not cytotoxic at 10 µg/ml and exhibited
dose response toxicity with maximum toxicity of 38% over the
control at 1000 µg/ml.
- Zymography demonstrated production of only MMP-9,
which showed a dose-dependent decreased expression, which was
abolished at 100 µg/ml of NS.
- Invasion through Matrigel was inhibited at 10,
50, 100, and 500 µg/ml by 66, 66, 87 and 100% respectively.
H&E staining did not indicate changes even at highest concentration
of NS.
Conclusions:
Our results suggest that NS is an excellent candidate for therapeutic
use in the treatment of pancreatic cancer, by inhibiting MMP expression,
invasion, and angiogenesis - all important promising parameters
for cancer prevention.
Comment:
Cancer of the pancreas is a highly lethal disease with the
poorest likelihood of survival among all major malignancies;
metastasis is associated with more than 80% of the cases.
This study demonstrated significant inhibition of the metastatic
parameters of MMP expression, invasion, and angiogenesis,
suggesting NS is an excellent candidate for therapeutic use
in the treatment of pancreatic cancer. |
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