Matrix Metalloproteinase-2 Inhibition and Invasion Potential in Human Chondrocytes by a natural anti-cancer formula - a Specific Mixture of Nutrients Containing Lysine, Proline, Ascorbic Acid and Epigallocatechin Gallate.

M.W. Roomi, S.P. Netke, V. Ivanov, M. Rath and A. Niedzwiecki

Presented at: American Association of Cancer Research Special Conference in Cancer Research: Proteases, Extracellular Matrix and Cancer, Hilton Head Island, South Carolina, Oct 9-13, 2002
Published in: Conference Proceedings: Abstarct B36

Cartilage erosion as well as variable degrees of synovial inflammation are two crucial features of osteoarthritis. Current thinking is that these changes are due to up-regulation of chondrocytes mediated matrix metalloproteinases (MMPs), which in turn lead to a breakdown of cartilage macromolecules.

We have been investigating different biological active components from natural products that inhibit MMPs activities. A natural anti-cancer formula, a specific mixture of nutrients and natural products containing lysine, proline, ascorbic acid and epigallocatechin gallate was formulated on the premise that such a combination of nutrients would exert a very potent synergistic effect on MMPs activities.

Recently, we have reported that a natural anti-cancer formula inhibits MMPs activity and invasion potential in a number of human cancer cell lines. In the present study we have investigated the effect of a natural anti-cancer formula on human chondrocytes, specifically on the expression of MMP-2, cell proliferation/cytotoxicity and matrix invasion potential. MMP-2 activity was assayed by zymography, invasion potential by the ablity to invade through reconstituted basement membrane (Matrigel) and cytotoxicity by MTT assay.

The results indicated that a natural anti-cancer formula inhibits the expression of MMP-2 in a dose dependent manner. The expression of MMP-2 was significantly inhibited at a concentration of 100ug/ml of a natural anti-cancer formula and virtually not detected at a concentration of 200ug/ml. In addition, it was also found that invasion of chondrocytes through Matrigel was inhibited by 50%, 85% and 95% at 10ug/ml, 100ug/ml and 200ug/ml, respectively. At 500 ug/ml the invasion was complete.

Interestingly, a natural anti-cancer formula was not toxic to chondrocytes even at a concentration of 200ug/ml. In fact, a natural anti-cancer formula exerted a cell prolifertive effect, a 70% increase in cell proliferation with 200ug/ml, 70% more over the control. These results demonstrate that a natural anti-cancer formula is very effective in inhibiting the expression of MMP-2 in chondrocytes and in preventing their ability to invade through Matrigel. Taking into account safety record of nutritional supplements and the encouraging results of this study with a natural anti-cancer formula, this nutrient combination should be considered a novel anti-inflammatory candidate for natural approach to inhibit MMP production and ECM degradation in osteoarthritis and other problems related to excessive cartilage degradation.