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:
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
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
was formulated on the premise that such a combination of nutrients
would exert a very potent synergistic effect on MMPs activities.
we have reported that a natural anti-cancer formula inhibits MMPs
activity and invasion potential in a number of human cancer cell lines.
investigated the effect of a natural anti-cancer formula on human
chondrocytes, specifically on the expression of MMP-2, cell proliferation/cytotoxicity
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
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,
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
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
production and ECM degradation in osteoarthritis and other problems
related to excessive cartilage degradation.