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Antitumor Effect of an anti-cancer nutrient synergy in Pancreatic Cancer Cell Line MIA Pa Ca-2

M.W. Roomi, V. Ivanov, M. Rath, and A. Niedzwiecki

Matthias Rath, Inc., Research and Development, Santa Clara, CA 95050

1. 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 an anti-cancer 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. The anti-cancer nutrient synergy also suppressed the growth of these tumors, without any adverse effects, in nude mice.

In the current study, we investigated the effect of an anti-cancer nutrient synergy in a relatively uncommon cancer, pancreatic cancer. Cancer of the pancreas continues to be a major unsolved health problem, causing approximately 28,000 deaths in the U.S. and 50,000 deaths in Europe each year. Pancreatic cancer is the fourth leading cause of cancer-related deaths in both men and women.

2. Objective:

We investigated the effect of an anti-cancer nutrient synergy on the pancreatic cancer cell line MIA PaCa-2 for viability, MMP expression, invasion, and morphology.

3. Composition of an anti-cancer nutrient synergy:

4. 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 observer by Hematoxylin and Eosin staining.

5. Results:

1. The anti-cancer nutrient synergy was not cytotoxic at 10 ug/ml and exhibited a dose-dependent toxicity, with maximum toxicity of 38% over the control at 1000 ug/ml.

Figure 1 - Effect of anti-cancer nutrient synergy on the Growth of Pancreatic Cancer Cell Line MIA Pa Ca-2 (24-hour MTT Assay)

2. Zymography demonstrated expression of only MMP-9, which showed a dose-dependent decreased expression that was abolished at 100 ug/ml of anti-cancer nutrient synergy.

Figure 2 - Effect of anti-cancer nutrient synergy on MMP-9 Expression by Pancreatic Cancer Cell Line MIA Pa Ca-2 1. Markers, 2. Control, 3.-7. Anti-cancer nutrient synergy 10, 50, 100, 500, 1000 mcg/ml

3. Invasion through Matrigel was inhibited at 10, 50, 100, and 500 ug/ml by 66%, 66%, 87%, and 100% respectively.

Figure 3A - Effect of anti-cancer nutrient synergy on Matrigel Invasion and Migration by Pancreatic Cell Line MIA Pa Ca-2

Figure 3B - Invasion Through Matrigel

4. H&E staining demonstrated no changes in morphology even at the highest concentrations of anti-cancer nutrient synergy.

Figure 4 - Effect of anti-cancer nutrient synergy on H&E Stains of Pancreatic Cancer Cells

6. Conclusions:

Our results suggest that the anti-cancer nutrient synergy 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.