Inhibitory effects of ascorbic acid, proline and lysine supplementation on Matrigel invasion by human breast cancer cells, MDA-MB231.
S Netke, Ph.D., V Ivanov , MD. Ph.D., W. Roomi, Ph. D., A Niedzwiecki, Ph. D., Matthias Rath, M.D.
Presented at: 19th Annual Miami Breast Cancer Conference, Miami
Beach, Florida, February 27 – March 3, 2002.
Worldwide, breast cancer is the most prevalent cancer in women. Metastasis potential and invasiveness of breast cancer are attributed to up-regulation of matrix metalloproteinases (MMPs).
In the current study, we studied the effect of a natural anti-cancer formula on invasive potential of human breast cancer cell lines. EF is a specific mixture of lysine, proline, ascorbic acid and epigallocatechin, which we have shown previously that have a very potent synergistic antitumor activity through inhibiting extracellular matix invasion by cancer cells.
In this study we tested effect of a natural anti-cancer formula on estrogen-receptor positive (ER+) MCF-7 and estrogen-receptor negative (ER-) MDA-MB-231 breast cancer cell lines. Metastatic parameters: expression of MMPs by zymography, cellular invasion through Matrigel and proliferation/cytotoxicity by MTT assay were studied. Invasion of MBA-MD-231 through matrigel was inhibited by 50%, 60% and 95% by 10, 50 and 100 ug/ml of EF respectively. EF was not toxic to MDA-MB-231 at 10ug/ml, showed slight toxicity at 100ug/ml.
However, it exhibited significant toxicity at 1000 ug/ml. Neither MMP-2 nor MMP-9 were detected by gelatinase zymography. In contrast, the natural anti-cancer formula was not toxic to MCF-7 at 10, 50, 100 and 500 ug/ml, and exhibited slight toxicity at 1000 ug/ml. Interestingly, MCF-7 was not invasive through Matrigel and did not express any MMP activity. These results suggest that the natural anti-cancer formula is valuable and promising candidate for ER- , MDA-MB-231 breast cancer cells. Further studies will be required for ER+ , MCF-7 breast cancer cells to determine the efficacy of a natural anti-cancer formula.
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