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A Specific Combination
of Ascorbic Acid, Lysine, Proline and Epigallocatechin Gallate
Inhibits Proliferation and Extracellular Matrix Invasion of Various
Human Cancer Cell Lines (2003)
Netke SP, Roomi MW, Roomi NW, Ivanov V, Niedzwiecki
A, Rath M.
Published in: Research Communications
in Pharmacology and Toxicology: Emerging Drugs, 2:37-5, 2003.
Abstract
We found that a specific combination of ascorbic
acid (AA, 100 µM), proline (P, 140 µM), and lysine
(L, 400 µM) had a significant anti-proliferative and anti-metastatic
effect against some human cancer cell lines in the breast (MDA-MB-231),
colon (HCT 116), and skin (melanoma, A2058). In the presence of
this nutrient combination, the invasion of extracellular matrix
by human breast cancer cells, melanoma cells, and colon cancer
cells was inhibited by 50%, 10%, and 30%, respectively. The addition
of Epigallocatechin Gallate (EGCG) further enhanced this nutritional
synergy and produced a more pronounced inhibitory effect on both
cellular proliferation and matrix invasion. The proliferation
of breast cancer cells (MDA-MB-231) in the presence of AA, P,
L and 20 µg/ml of EGCG was reduced to 74%. The proliferation
of colon cancer cells (HCT 116) was reduced to 69%, compared to
the non-supplemented medium. The increase in concentration of
EGCG to 50 µg/ml did not cause much further reduction in
the cell number of breast cancer cells, but it did reduce the
proliferation of colon cancer cells to 4.6% and melanoma cells
to 30% of the control. Matrigel invasion by breast cancer cells
(MDA-MB-231) and human melanoma cells (A2058) in the presence
of AA, P, L and 20 µg/ml of EGCG was stopped completely.
At a similar concentration, the invasion of colon cancer cells
was reduced to 24.9%. However, the expression of matrix metalloproteinases
(MMPs) -2 and -9 was not altered by this nutrient combination
in melanoma cells as visualized by gelatinase zymography. MMP-2
and MMP-9 were significantly inhibited by EGCG in a dose-dependent
fashion; L, P, and AA had no additional effect. Thus, the combination
of AA, P, L and EGCG shows great potential for the control of
cancer using a safe and multi-targeted approach.
Comment:
This study demonstrated significant anti-proliferative and
anti-metastatic effects in vitro against some human cancer
cell lines (breast, colon, and melanoma) using a specific
combination of ascorbic acid, proline, and lysine. The addition
of epigallocatechin gallate (EGCG) to the nutrient mixture
enhanced the inhibitory effect on both cellular proliferation
and invasion. These results are significant in showing the
great potential of the control of cancer growth and metastasis
using a safe nutrient approach. |

Legend:
LPA = Lysine (L, 400 µM) + Proline (P, 140 µM) + Ascorbic
Acid (A, 100 µM)
EGCG = Epigallocatechin Gallate 20 µg/ml
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