M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
FASEB, San Francisco, CA, April 1-5, 2006
The FASEB Journal, Abstract #107
Matrix metalloproteinase (MMP) expression and production are associated with advanced tumor stage and contribute to tumor progression, invasion and metastasis. A unique non-toxic nutrient mixture (NM) consisting of lysine, proline, ascorbic acid and green tea extract has been shown to exhibit anti-tumor activity against a number of cancer cell lines both in vivo and in vitro.
In this study we sought to examine the effect of NM on human acute Jurkat T cells on proliferation, MMP secretion and invasion through Matrigel.
Methods and Materials:
Human T Jurkat cells (ATCC) were grown in RPMI-1640 medium with 10% fetal bovine serum and antibiotics and treated with NM at 0, 10, 50, 100, 500 and 1000 µg/ml concentration in triplicate at each dose. Cell proliferation was assessed by counting cells stained with Trypan blue, invasion was evaluated through Matrigel, and MMPs by gelatinase zymography. Cells were also treated with PMA to induce MMP-9 activity.
NM was not toxic to cells at 100 µg/ml concentration and exhibited antiproliferative effect at 500 µg/ml concentration. Zymography demonstrated a faint band corresponding to MMP-9 and enhanced activity after PMA stimulation. NM showed a dose dependent inhibition in MMP-9 activity with virtual total inhibition at 500 µg/ml concentration. Matrigel invasion was significantly reduced at 500 µg /ml and totally blocked at 1000 µg/ml NM.
Our results demonstrate that NM is a promising new therapeutic agent for acute leukemia, and is potential candidate for human trials.
Cellular production of matrix metalloproteinases contributes to tumor progression, invasion and metastasis. We investigated whether cellular invasion and production of MMPs by a leukemia cell line, Jurkat T, can be affected by a unique nutrient mixture (NM) consisting primarily of lysine, proline, ascorbic acid and green tea extract. We have demonstrated previously (Harakeh et al. 2006) that this nutrient mixture was effective in inducing apoptosis in this and other leukemia cell lines. In addition, it has been shown to exhibit anti-tumor activity both in vitro and in vivo against a number of cancer cell lines. NM exhibited antiproliferative effect on human acute Jurkat T cells at 500?g/ml, and dose-dependent inhibition of MMP-9 secretion and Matrigel invasion, with total blockage of MMP-9 secretion at 500 ?g/ml NM and of invasion at 1000 ?g/ml NM. These results are significant as they confirm previous data and indicate that NM is potentially a promising therapeutic agent for acute leukemia.