A specific combination of ascorbic acid, lysine, proline and epigallocatechin gallate inhibits proliferation and extracellular matrix Invasion of various human cancer cell lines

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

Research Communications in Pharmacology and Toxicology, Emerging Drugs 2003; Vol. II, IV37-IV50

We found that a specific combination of ascorbic acid (AA, 100µM), proline (P, 140 µM) and lysine (L, 400 µM) had a significant antiproliferative and antimetastatic effect against some human cancer cell lines, breast (MDA-MB-231), colon (HCT116) and skin (melanoma, A2058). In the presence of this nutrient combination the invasion of the extracellular matrix by human breast cancer cells, melanoma cells and colon cancer cells was inhibited by 50%, 10% and 30% respectively. Addition of epigallocatechin gallate (EGCG) further enhanced this nutritional synergy producing 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 20µg/ml of EGCG was reduced to 74% and colon cancer cells HCT116 to 69% compared to the unsupplemented medium. The increase in concentration of EGCG to 50µg/ml did not cause much further reduction in the number of breast cancer cells. However it reduced proliferation of colon cancer cells to 4,6% and melanoma cells to 30% of the control. Matrigel invasion by breast cancer cells and human melanoma cells in the presence of AA, P, L and 20µg/ml of EGCG was stopped completely. At a similar concentration, invasion by 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 manner, and L, P, AA have no additional effect. Thus the combination of AA, P, L and EGCG shows great potential for control of cancer using a safe and multi-targeted approach.

Key Words: 
Antiproliferative and antimetastatic effect, breast cancer (MDA-MB-231), colon cancer (HCT116), epigallocatechin gallate, gelatinase zymography, matrix metalloproteinases (MMPs) –2 and –9, proliferation of cancer, skin melanoma (A2058), specific combination of ascorbic acid, proline, and lysine.

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