| Antileukemic
Effect of a Novel Nutrient Mixture on Human JURKAT T Cells
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara,
CA 95050
Presented at: FASEB, San Francisco, CA, April
1-5, 2006
Published in: The FASEB Journal, Abstract #107
Abstract
Introduction:
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.
Objective:
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.
Results:
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.
Conclusions:
Our results demonstrate that NM is a promising new therapeutic
agent for acute leukemia, and is potential candidate for human
trials.
Comment:
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. |
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